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Sample records for vulnerable atherosclerotic plaque

  1. Mechanical model of vulnerable atherosclerotic plaque rupture

    Institute of Scientific and Technical Information of China (English)

    SU; Haijun; ZHANG; Mei; ZHANG; Yun

    2004-01-01

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

  2. Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

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    Eugenio Picano

    2015-05-01

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

  3. Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque

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

    2011-01-01

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

  4. Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

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    Hamblin, Michael R.; Tawakol, Ahmed; Castano, Ana P.; Gad, Faten; Zahra, Touqir; Ahmadi, Atosa; Stern, Jeremy; Ortel, Bernhard; Chirico, Stephanie; Shirazi, Azadeh; Syed, Sakeena; Muller, James E.

    2003-06-01

    Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  6. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

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    Sara Gargiulo

    2016-09-01

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

  7. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

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    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

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

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

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

    2017-01-01

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

  9. Vulnerable atherosclerotic carotid plaque evaluation by ultrasound, computed tomography angiography, and magnetic resonance imaging: an overview.

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    Naim, Cyrille; Douziech, Maxime; Therasse, Eric; Robillard, Pierre; Giroux, Marie-France; Arsenault, Frederic; Cloutier, Guy; Soulez, Gilles

    2014-08-01

    Ischemic syndromes associated with carotid atherosclerotic disease are often related to plaque rupture. The benefit of endarterectomy for high-grade carotid stenosis in symptomatic patients has been established. However, in asymptomatic patients, the benefit of endarterectomy remains equivocal. Current research seeks to risk stratify asymptomatic patients by characterizing vulnerable, rupture-prone atherosclerotic plaques. Plaque composition, biology, and biomechanics are studied by noninvasive imaging techniques such as magnetic resonance imaging, computed tomography, ultrasound, and ultrasound elastography. These techniques are at a developmental stage and have yet to be used in clinical practice. This review will describe noninvasive techniques in ultrasound, magnetic resonance imaging, and computed tomography imaging modalities used to characterize atherosclerotic plaque, and will discuss their potential clinical applications, benefits, and drawbacks. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  10. 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

    . However, refuting the hypothesis, the concentrations of the suPAR forms were not higher in patients with short intervals between clinical event and blood sampling compared with those with long intervals. Age, inflammatory markers and diabetes were confounding factors independently associated with su......PAR forms. CONCLUSION:: Circulating suPAR forms are probably not useful biomarkers of atherosclerotic plaque vulnerability....

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

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    David De Wilde

    2015-06-01

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

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

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    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.

  14. Biomarkers of atherosclerotic plaque vulnerability and their clinical significance

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    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

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

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    Leon J Schurgers

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

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

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

    2015-11-01

    This study's goal was to assess the diagnostic value of the USPIO-(ultra-small superparamagnetic iron oxide) enhanced magnetic resonance imaging (MRI) in detection of vulnerable atherosclerotic plaques in abdominal aorta in experimental atherosclerosis. Thirty New Zealand rabbits were randomly divided into two groups, Group A and Group B. Each group comprised 15 animals which were fed with high cholesterol diet for 8 weeks and then subjected to balloon-induced endothelial injury of the abdominal aorta. After another 8 weeks, animals in Group B received adenovirus carrying p53 gene that was injected through a catheter into the aortic segments rich in plaques. Two weeks later, all rabbits were challenged with the injection of Chinese Russell's viper venom and histamine. Pre-contrast images and USPIO-enhanced MRI images were obtained after pharmacological triggering with injection of USPIO for 5 days. Blood specimens were taken for biochemical and serological tests at 0 and 18 weeks. Abdominal aorta was histologically studied. The levels of serum ICAM-1 and VCAM-1 were quantified by ELISA. Vulnerable plaques appeared as a local hypo-intense signal on the USPIO-enhanced MRI, especially on T2*-weighted sequences. The signal strength of plaques reached the peak at 96 h. Lipid levels were significantly (p < 0.05) higher in both Group A and B compared with the levels before the high cholesterol diet. The ICAM-1 and VCAM-1 levels were significantly (p < 0.05) higher in Group B compared with Group A. The USPIO-enhanced MRI efficiently identifies vulnerable plaques due to accumulation of USPIO within macrophages in abdominal aorta plaques.

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

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

    2000-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

    SU HaiJun; ZHANG PengFei; OHEN WenQiang; ZHANG Mei; ZHANG Yun

    2008-01-01

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

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

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

    2016-10-08

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

  20. 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.

  1. 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)

  2. 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....

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

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    HUANG Yan

    2012-06-01

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

  5. Selective inhibition of PI3K/Akt/mTOR signaling pathway regulates autophagy of macrophage and vulnerability of atherosclerotic plaque.

    Directory of Open Access Journals (Sweden)

    Chungang Zhai

    Full Text Available Macrophage infiltration contributes to the instability of atherosclerotic plaques. In the present study, we investigated whether selective inhibition of PI3K/Akt/mTOR signaling pathway can enhance the stability of atherosclerotic plaques by activation of macrophage autophagy. In vitro study, selective inhibitors or siRNA of PI3K/Akt/mTOR pathways were used to treat the rabbit's peritoneal primary macrophage cells. Inflammation related cytokines secreted by macrophages were measured. Ultrastructure changes of macrophages were examined by transmission electron microscope. mRNA or protein expression levels of autophagy related gene Beclin 1, protein 1 light chain 3 II dots (LC3-II or Atg5-Atg12 conjugation were assayed by quantitative RT-PCR or Western blot. In vivo study, vulnerable plaque models were established in 40 New Zealand White rabbits and then drugs or siRNA were given for 8 weeks to inhibit the PI3K/Akt/mTOR signaling pathway. Intravascular ultrasound (IVUS was performed to observe the plaque imaging. The ultrastructure of the abdominal aortic atherosclerosis lesions were analyzed with histopathology. RT-PCR or Western blot methods were used to measure the expression levels of corresponding autophagy related molecules. We found that macrophage autophagy was induced in the presence of Akt inhibitor, mTOR inhibitor and mTOR-siRNA in vitro study, while PI3K inhibitor had the opposite role. In vivo study, we found that macrophage autophagy increased significantly and the rabbits had lower plaque rupture incidence, lower plaque burden and decreased vulnerability index in the inhibitors or siRNA treated groups. We made a conclusion that selective inhibition of the Akt/mTOR signal pathway can reduce macrophages and stabilize the vulnerable atherosclerotic plaques by promoting macrophage autophagy.

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

    DEFF Research Database (Denmark)

    Mahmood, Badar; Ewertsen, C; Carlsen, Jørn

    2016-01-01

    to distinguish between vulnerable and stable plaques. The aim of this paper is to provide an overview of the literature on vascular elastography. A systematic search of the available literature for studies using elastography for assessing atherosclerotic plaques was conducted using the MEDLINE, Embase, Cochrane...... 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...

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

    Directory of Open Access Journals (Sweden)

    Giampaolo Niccoli

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  9. Lipoprotein (a) is related to coronary atherosclerotic burden and a vulnerable plaque phenotype in angiographically obstructive coronary artery disease.

    Science.gov (United States)

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

    2016-03-01

    Lipoprotein Lp(a) has been shown to be an independent risk factor for coronary artery disease (CAD). However, its association with CAD burden in patients with ACS is largely unknown, as well as the association of Lp(a) with lipid rich plaques prone to rupture. We aim at assessing CAD burden by coronary angiography and plaque features including thin cap fibroatheroma (TCFA) by optical coherence tomography (OCT) in consecutive patients presenting with acute coronary syndrome (ACS) and obstructive CAD along with serum Lp(a) levels. This study comprises an angiographic and an OCT cohort. A total of 500 ACS patients (370 men, average age 66 ± 11) were enrolled for the angiographic cohort and 51 ACS patients (29 males, average age 65 ± 11) were enrolled for the OCT cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index. OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. In the angiographic cohort, at multivariate analysis, Lp(a) was a weak independent predictor of Sullivan score (p < 0.0001), stenosis score (p < 0.0001) and extent index (p < 0.0001). In the OCT cohort, patients with higher Lp(a) levels (≥ 30 md/dl) compared to patients with lower Lp(a) levels (<30 md/dl) exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (67% vs. 27%; P = 0.02), a wider lipid arc (135 ± 114 vs 59 ± 111; P = 0.03) and a higher prevalence of TCFA (38% vs. 10%; P = 0.04). Among patients with ACS, raised Lp(a) levels are associated with an increased atherosclerotic burden and it identifies a subset of patients with features of high risk coronary atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. MRI-determined carotid artery flow velocities and wall shear stress in a mouse model of vulnerable and stable atherosclerotic plaque.

    Science.gov (United States)

    van Bochove, Glenda S; Straathof, Roel; Krams, Rob; Nicolay, Klaas; Strijkers, Gustav J

    2010-04-01

    We report here on the pre-clinical MRI characterization of an apoE-/- mouse model of stable and vulnerable carotid artery atherosclerotic plaques, which were induced by a tapered restriction (cast) around the artery. Specific focus was on the quantification of the wall shear stress, which is considered a key player in the development of the plaque phenotype. In vivo MRI was performed at 9.4 T. The protocol consisted of time-of-flight angiography, high-resolution T1- and T2-weighted black-blood imaging and phase-contrast flow velocity imaging as function of time in the cardiac cycle. Wall shear stress was determined by fitting the flow profile to a quadratic polynomial. Time-of-flight angiography confirmed preservation of blood flow through the carotid arteries in all cases. T1- and T2-weighted MRI resulted in high-resolution images in which the position of the cast, luminal narrowing introduced by cast and plaque, as well as the arterial wall could be well identified. Laminar flow with low wall shear stress (11.2+/- 5.2 Pa) was measured upstream to the cast at the position of the vulnerable plaque. Downstream to the cast at the position of the stable plaque, the apparent velocities were low, which is consistent with vortices and an oscillatory nature of the flow. Flow velocities and wall shear stress were successfully measured in this mouse model of stable and unstable plaque. The presented tools can be used to provide valuable insights in the pathogenesis of atherosclerosis.

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Quan-ming Zhao

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

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

    Science.gov (United States)

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

    2016-12-09

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

  15. Magnetic force microscopy of atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Alexeeva T.A.

    2014-03-01

    Full Text Available In this work by methods of scanning probe microscopy, namely by atomic force microscopy and magnetic force microscopy the fragments of atherosclerotic plaque section of different nature were investigated. The fragments of atherosclerotic vessels with elements of immature plaque were taken during the coiled artery bypass surgery by alloprosthesis. As the result of investigation we found magnetically ordered phase of endogenous origin in the fragment of solid plaque of mixed structure. This phase is presents biogenic magnetic nanoparticles and their clusters with average size characteristic of 200-400 nm.

  16. [Is regression of atherosclerotic plaque possible?

    Science.gov (United States)

    Páramo, José A; Civeira, Fernando

    As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion ('angiographic paradox'). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilizing effects. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 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.

  18. Lipidome of atherosclerotic plaques from hypercholesterolemic rabbits.

    Science.gov (United States)

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

    2014-12-15

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

  19. Lipidome of Atherosclerotic Plaques from Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Lazar A. Bojic

    2014-12-01

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

  20. Vaporization of atherosclerotic plaques by spark erosion

    NARCIS (Netherlands)

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

    1985-01-01

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

  1. Mathematical models for atherosclerotic plaque evolution

    NARCIS (Netherlands)

    Bulelzai, M.A.K.

    2013-01-01

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

  2. Current status of vulnerable plaque detection.

    LENUS (Irish Health Repository)

    Sharif, Faisal

    2012-02-01

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

  3. Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

    Directory of Open Access Journals (Sweden)

    P. Assemat

    2014-07-01

    Full Text Available Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical modelling. The geometries are digitalised from synchrotron imaging and realistic pulsatile blood flow is considered under rigid wall assumptions. Two cases are considered; arteries with and without plaque. Mice that are fed under fat diet present plaques in the aortic arch whose size is dependent on the number of weeks under the diet. The plaque distribution in the region is however relatively constant through the different samples. This result underlines the influence of the geometry and consequently of the wall shear stresses for plaque formation with plaques growing in region of relative low shear stresses. A discussion of the flow field in real geometry in the presence and absence of plaques is conducted. The presence of plaques was shown to alter the blood flow and hence WSS distribution, with regions of localised high WSS, mainly on the wall of the brachiocephalic artery where luminal narrowing is most pronounced. In addition, arch plaques are shown to induce recirculation in the blood flow, a phenomenon with potential influence on the progression of the plaques. The oscillatory shear index and the relative residence time have been calculated on the geometry with plaques to show the presence of this recirculation in the arch, an approach that may be useful for future studies on plaque progression.

  4. Atherosclerotic Aortic Plaques Detected by Transesophageal Echocardiography

    Institute of Scientific and Technical Information of China (English)

    赵云; 朱文玲; 倪超; 郭丽琳; 曾勇; 方理刚

    2002-01-01

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

  5. 冠状动脉内动脉粥样硬化易损斑块的检测和治疗进展%Advances of evaluation and treatment of atherosclerotic vulnerable plaque within coronary artery

    Institute of Scientific and Technical Information of China (English)

    黄震华

    2011-01-01

    The characteristics of vulnerable plaque are thin fibrous cap, high proportional atherosclerotic core, increased plaque inflammation, and intraplaque hemorrhage. Vulnerable plaques are apt to rupture,causing platelet adhesion, platelet aggregation, and thrombosis. Vulnerable plaque rupture within coronary artery may induce acute coronary events. Intravascular ultrasounds, virtual histology, palpography, optical coherence tomography, intravascular magnetic resonance imaging, angioscopy, and spectroscopy are currently methods for detecting vulnerable plaque. Drugs, regional therapy, and stents are main strategies for treating vulnerable plaque nowadays.%易损斑块的特征是纤维帽薄、动脉粥样硬化斑块核心比例高、斑块炎症明显及伴斑块内出血.易损斑块易发生破裂,引起血小板黏附聚集和血栓形成.冠状动脉内易损斑块破裂可引起急性冠脉事件.血管内超声、虚拟组织学成像、激应图成像、光学相干断层成像、血管内磁共振显像、血管镜、分光镜等是目前检测易损斑块的主要手段.对冠状动脉内易损斑块应积极干预,药物、局部治疗、安放支架等是目前治疗易损斑块的主要方法.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    a challenge. RESULTS: To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2...

  7. A comparative study on plaque vulnerability using constitutive equations.

    Science.gov (United States)

    Karimi, A; Navidbakhsh, M; Faghihi, S

    2014-03-01

    Atherosclerosis is the most serious and common form of cardiovascular disease in which plaque builds up inside the arteries. Peak plaque stress is considered as the main reason for plaque rupture, which results in heart attack and stroke. In the current research, the finite element method is used to anticipate plaque vulnerability, using human samples. A total of 23 healthy and atherosclerotic human coronary arteries (14 healthy and 9 atherosclerotic) were removed within 5 h postmortem. The samples were mounted on a uniaxial tensile test machine and the obtained mechanical properties were used in finite element models. The peak plaque stresses for the Ogden hyperelastic model were compared to the Mooney-Rivlin and Neo-Hookean outcomes. The results indicated that hypocellular plaque in all three models has the highest stress values compared to the cellular and calcified ones and, as a result, is quite prone to rupture. The calcified plaque type, in contrast, has the lowest stress values and remains stable. The results can be used in plaque vulnerability prediction and have clinical implications for interventions and surgeries such as balloon-angioplasty, cardiopulmonary bypass and stenting.

  8. Coronary spasm, a pathogenic trigger of vulnerable plaque rupture

    Institute of Scientific and Technical Information of China (English)

    WANG Li-xin; L(U) Shu-zheng; ZHANG Wei-jun; SONG Xian-tao; CHEN Hui; ZHANG Li-jie

    2011-01-01

    Objective This coronary artery spasm review aimed to explore the most possible pathogenic trigger mechanism of vulnerable plaque rupture.Data sources Data used in this coronary artery spasm review were mainly from Medline and Pubmed in English.Study selection These reports from major review on coronary artery spasm.and these research included coronary artery conception,pathogenesis of spasm,mechanisms of plaque rupture,epidemiological evidence,clinical manifestation and the relationship between coronary artery spasm and vulnerable plaque rupture.Results Coronary artery spasm is somehow related to the presence of atherosclerotic intima disease in the coronary artery.However,chronic low-grade inflammation causes coronary vessel smooth muscle cell hypersensitivity,which can directely cause coronary artery spasm.Myocardial infarction and sudden cardiac death may be initiated by a sudden intense localized contraction of coronary artery smooth muscle.Conclusion Coronary artery spasm may be one trigger that can initiate and exacerbate vulnerable plaque rupture.

  9. 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.

  10. 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.

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

    LENUS (Irish Health Repository)

    Maher, Eoghan

    2009-12-11

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  15. Multispectral optoacoustic tomography resolves smart probe activation in vulnerable plaques

    Science.gov (United States)

    Razansky, Daniel; Harlaar, Niels J.; Hillebrands, Jan-Luuk; Taruttis, Adrian; Herzog, Eva; Zeebregts, Clark; van Dam, Goitzen; Ntziachristos, Vasilis

    2011-03-01

    In this work, we show, for the first time to our knowledge, that multispectral optoacoustic tomography (MSOT) can deliver high resolution images of activatable molecular probe's distribution, sensitive to matrix metalloproteinases (MMP), deep within optically scattering human carotid specimen. It is further demonstrated that this method can be used in order to provide accurate maps of vulnerable plaque formations in atherosclerotic disease. Moreover, optoacoustic images can simultaneously show the underlining plaque morphology for accurate localization of MMP activity in three dimensions. This performance directly relates to small animal screening applications and to clinical potential as well.

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

    Science.gov (United States)

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

    2016-10-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth...... in the ground truth used for training: I) soft labels are created by Gaussian blurring of the original binary histology segmentations to reduce weights at the boundaries between components, and are weighted by the estimated registration accuracy of the histology and in vivo imaging data (measured by overlap......), II) samples are weighted by the local contour distance of the lumen and outer wall between histology and in vivo data, and III) 10% of each class is rejected by Gaussian outlier rejection. Classification was evaluated on the relative volumes (% of tissue type in the vessel wall) for calcified...

  18. Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression

    NARCIS (Netherlands)

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

    2015-01-01

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

  19. Chemokine Receptor 7 Knockout Attenuates Atherosclerotic Plaque Development

    NARCIS (Netherlands)

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

    2010-01-01

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

  20. Association between chlamydia pneumoniae infection and carotid atherosclerotic plaques

    Directory of Open Access Journals (Sweden)

    Fereshteh Ashtari

    2007-08-01

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

  1. 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.

  2. Myeloperoxidase-oxidized high density lipoprotein impairs atherosclerotic plaque stability by inhibiting smooth muscle cell migration.

    Science.gov (United States)

    Zhou, Boda; Zu, Lingyun; Chen, Yong; Zheng, Xilong; Wang, Yuhui; Pan, Bing; Dong, Min; Zhou, Enchen; Zhao, Mingming; Zhang, Youyi; Zheng, Lemin; Gao, Wei

    2017-01-10

    High density lipoprotein (HDL) has been proved to be a protective factor for coronary heart disease. Notably, HDL in atherosclerotic plaques can be nitrated (NO2-oxHDL) and chlorinated (Cl-oxHDL) by myeloperoxidase (MPO), likely compromising its cardiovascular protective effects. Here we determined the effects of NO2-oxHDL and Cl-oxHDL on SMC migration using wound healing and transwell assays, proliferation using MTT and BrdU assays, and apoptosis using Annexin-V assay in vitro, as well as on atherosclerotic plaque stability in vivo using a coratid artery collar implantation mice model. Our results showed that native HDL promoted SMC proliferation and migration, whereas NO2-oxHDL and Cl-oxHDL inhibited SMC migration and reduced capacity of stimulating SMC proliferation as well as migration, respectively. OxHDL had no significant influence on SMC apoptosis. In addition, we found that ERK1/2-phosphorylation was significantly lower when SMCs were incubated with NO2-oxHDL and Cl-oxHDL. Furthermore, transwell experiments showed that differences between native HDL, NO2-oxHDL and Cl-oxHDL was abolished after PD98059 (MAPK kinase inhibitor) treatment. In aortic SMCs from scavenger receptor BI (SR-BI) deficient mice, differences between migration of native HDL, NO2-oxHDL and Cl-oxHDL treated SMCs vanished, indicating SR-BI's possible role in HDL-associated SMC migration. Importantly, NO2-oxHDL and Cl-oxHDL induced neointima formation and reduced SMC positive staining cells in atherosclerotic plaque, resulting in elevated vulnerable index of atherosclerotic plaque. These findings implicate MPO-catalyzed oxidization of HDL may contribute to atherosclerotic plaque instability by inhibiting SMC proliferation and migration through MAPK-ERK pathway which was dependent on SR-BI.

  3. Electrochemical Impedance Spectroscopy to Characterize Inflammatory Atherosclerotic Plaques

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    KAUST Repository

    Hossain, Shaolie S.

    2010-01-01

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

  6. Multimodal nonlinear imaging of atherosclerotic plaques differentiation of triglyceride and cholesterol deposits

    Directory of Open Access Journals (Sweden)

    Christian Matthäus

    2014-09-01

    Full Text Available Cardiovascular diseases in general and atherothrombosis as the most common of its individual disease entities is the leading cause of death in the developed countries. Therefore, visualization and characterization of inner arterial plaque composition is of vital diagnostic interest, especially for the early recognition of vulnerable plaques. Established clinical techniques provide valuable morphological information but cannot deliver information about the chemical composition of individual plaques. Therefore, spectroscopic imaging techniques have recently drawn considerable attention. Based on the spectroscopic properties of the individual plaque components, as for instance different types of lipids, the composition of atherosclerotic plaques can be analyzed qualitatively as well as quantitatively. Here, we compare the feasibility of multimodal nonlinear imaging combining two-photon fluorescence (TPF, coherent anti-Stokes Raman scattering (CARS and second-harmonic generation (SHG microscopy to contrast composition and morphology of lipid deposits against the surrounding matrix of connective tissue with diffraction limited spatial resolution. In this contribution, the spatial distribution of major constituents of the arterial wall and atherosclerotic plaques like elastin, collagen, triglycerides and cholesterol can be simultaneously visualized by a combination of nonlinear imaging methods, providing a powerful label-free complement to standard histopathological methods with great potential for in vivo application.

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

    Science.gov (United States)

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

    2016-04-01

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

  8. Research progress of noninvasive high - resolution magnetic resonance imaging in carotid atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Peng GAO

    2017-07-01

    Full Text Available Carotid atherosclerotic stenosis is closely related to recurrent ischemic stroke. Currently, therapies for carotid artery stenosis are mainly intensive medication or surgery, including carotid artery stenting (CAS and carotid endarterectomy (CEA. The prevention of stroke lies in identifying risk factors for carotid artery stenosis, screening patients with high risk of recurrent stroke, so as to benefit from medication or surgery. However, therapeutic schedule is formulated only according to the degrees of carotid artery stenosis, and there lacks of individualized treatment. Recently, new imaging modalities, such as noninvasive high.resolution MRI (HRMRI could detect the vulnerability of carotid atherosclerotic plaque. Compared with the degree of carotid artery stenosis measured by conventional DSA, noninvasive HRMRI can precisely predict the risk of ipsilateral stroke according to plaque morphology, so as to guide individualized treatment. DOI: 10.3969/j.issn.1672-6731.2017.05.012

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

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

  10. Endogenous activated angiotensin-(1-7) plays a protective effect against atherosclerotic plaques unstability in high fat diet fed ApoE knockout mice.

    Science.gov (United States)

    Yang, Jianmin; Yang, Xiaoyan; Meng, Xiao; Dong, Mei; Guo, Tao; Kong, Jing; Zhang, Kai; Zhang, Yun; Zhang, Cheng

    2015-04-01

    We recently found that exogenous angiotensin-(1-7) [Ang-(1-7)] inhibits Angiotensin II (Ang-II)-induced atherosclerotic lesion formation and enhances plaque stability. Our objective was to evaluate the role of endogenous activated Ang-(1-7) during atherosclerosis. In mice, the effects of endogenous Ang-(1-7) on atherogenesis in early stage and plaque stability in late stage were observed in ApoE knockout (ApoE-/-) mice fed with a high fat diet. Blockage of endogenous Ang-(1-7) with A779, an Ang-(1-7) antagonist, did not increase early plaque lesion formation, however, it remarkably enhanced contents of lipids and macrophages and decreased contents of vascular smooth muscle cells (VSMCs) and collagens in late lesions. The expressions of proinflammatory cytokines, and the expressions and activities of matrix metalloproteinases were significantly elevated in A779-treated group than those in vehicle-treated group in late lesions. Exogenous Ang-(1-7) treatment attenuated early atherosclerotic plaque formation and enhanced late plaques stability in this model. The contents of Ang-II and Ang-(1-7) and activity of ACE2 in late atherosclerotic plaques were higher than those of early atherosclerotic lesions. Endogenous activated Ang-(1-7) enhanced late atherosclerotic plaques stability but did not affect early atherosclerotic plaque formation. Therapies to elevate endogenous Ang-(1-7) may be a potentially effective approach to attenuate atherosclerotic plaques vulnerability. Copyright © 2015. Published by Elsevier Ireland Ltd.

  11. 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

  12. Progression and regression of the atherosclerotic plaque.

    Science.gov (United States)

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

    1995-08-01

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

  13. 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......-rich lipoproteins predict echo-lucency of carotid plaques, which is associated with increased plaque Lipid content, Because echo-lucency has been associated with a high incidence of brain infarcts on CT scans, triglyceride-rich lipoproteins may predict a plaque type particularly vulnerable to rupture....... carotid plaque echo-lucency and that echo-lucency predicts a high plaque lipid content. Methods and Results-The study included 137 patients with neurological symptoms and greater than or equal to 50% stenosis of the relevant carotid artery, High-resolution B-mode ultrasound images of carotid plaques were...

  14. 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......-rich lipoproteins predict echo-lucency of carotid plaques, which is associated with increased plaque Lipid content, Because echo-lucency has been associated with a high incidence of brain infarcts on CT scans, triglyceride-rich lipoproteins may predict a plaque type particularly vulnerable to rupture....... carotid plaque echo-lucency and that echo-lucency predicts a high plaque lipid content. Methods and Results-The study included 137 patients with neurological symptoms and greater than or equal to 50% stenosis of the relevant carotid artery, High-resolution B-mode ultrasound images of carotid plaques were...

  15. A role for archaeal organisms in development of atherosclerotic vulnerable plaques and myxoid matrices Um papel para organismos de arqueia no desenvolvimento de placas ateroscleróticas vulner��veis e matriz mixomatosa

    OpenAIRE

    2006-01-01

    PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulner...

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

    Directory of Open Access Journals (Sweden)

    Qian Di

    2012-03-01

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

  17. Vulnerable Plaques, Inflammation and Newer Imaging Modalities

    Directory of Open Access Journals (Sweden)

    Bhatia V

    2003-01-01

    Full Text Available Currently, inflammation is considered to be the central player in the pathogenesis of atherosclerosis. It leads to the formation of multiple plaques in the arterial beds including coronary vasculature. Recent studies using the latest imaging techniques have shown that in patients with acute coronary syndromes (ACS multiple plaques are ruptured and have thrombus formation on them. Various factors make these plaques unstable, these include structural components of plaque like thin fibrous cap, high lipid content of the plaque core and inflammation, both localized and generalized. It has been shown that most of the ACS are caused by plaques causing non-critical stenosis as seen on traditional X-ray angiography. Also, the phenomenon of remodelling makes angiography a poor technique for plaque visualization. Hence newer modalities are required to identify these 'vulnerable plaques'. Intravascular ultrasound (IVUS, thermography and Magnetic Resonance Imaging (MRI are a few such promising techniques. Here we review the invasive and non-invasive modalities that can be helpful in the identification of these plaques before they become unstable and cause ACS, and also the available therapies to stabilize these plaques.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kalanuria AA

    2012-09-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Pleunie van den Borne

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

  3. Local effects of atherosclerotic plaque on arterial distensibility.

    Science.gov (United States)

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

    2001-11-01

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

  4. Intracoronary Thermography: a vulnerable Plaque Detection Technique?

    NARCIS (Netherlands)

    A.G. ten Have (Anna)

    2006-01-01

    textabstractThe studies reported in this thesis were performed to answer the central question: can intracoronary thermography be used for vulnerable plaque detection? To answer this question, we have identified parameters that influence intracoronary thermography measurements, and have studied to w

  5. 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 with...

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

    Directory of Open Access Journals (Sweden)

    Higuchi Maria L.

    2002-01-01

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

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

    Science.gov (United States)

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

    2011-07-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

  9. Noninvasive diagnosis of vulnerable coronary plaque

    Science.gov (United States)

    Pozo, Eduardo; Agudo-Quilez, Pilar; Rojas-González, Antonio; Alvarado, Teresa; Olivera, María José; Jiménez-Borreguero, Luis Jesús; Alfonso, Fernando

    2016-01-01

    Myocardial infarction and sudden cardiac death are frequently the first manifestation of coronary artery disease. For this reason, screening of asymptomatic coronary atherosclerosis has become an attractive field of research in cardiovascular medicine. Necropsy studies have described histopathological changes associated with the development of acute coronary events. In this regard, thin-cap fibroatheroma has been identified as the main vulnerable coronary plaque feature. Hence, many imaging techniques, such as coronary computed tomography, cardiac magnetic resonance or positron emission tomography, have tried to detect noninvasively these histomorphological characteristics with different approaches. In this article, we review the role of these diagnostic tools in the detection of vulnerable coronary plaque with particular interest in their advantages and limitations as well as the clinical implications of the derived findings. PMID:27721935

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

    Science.gov (United States)

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

    2005-08-01

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

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

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    that compared to conventional B-mode imaging MACI features reduced image speckle and better definition of tissue interfaces. The point spread function (PSF) for MACI was investigated when scanning through water and through an inhomogeneous tissue mimicking medium and compared to the PSF for conventional imaging...... definition of the interfaces in the cases where one or more of the beams had near-normal incidence on the interface, i.e. an improved visualization over an angular range of interface orientations roughly corresponding to the range of beam angles used. The speckle statistics and the speckle reduction have...... consistent definition of the remaining lumen in the arteries and a less noisy depiction of the reflectivity inside the plaque deposits and the vessel wall. In conclusion, Multi-Angle Compound Imaging appears to be a promising imaging modality for improving the diagnosis of atherosclerotic disease...

  12. 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.)

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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, PGLUT-1, CD68, cathepsin K, and HK2 gene expression as independent predictive variables of FDG accumulation calculated...... as SUVmax (R=0.30, PGLUT-1, HK2, CD68, and cathepsin K remained in both multivariate models and thus provided independent information regarding FDG uptake. We suggest that FDG uptake is a composite indicator of macrophage load, overall inflammatory activity and collagenolytic plaque...

  15. Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining.

    Science.gov (United States)

    Scharlach, Constantin; Kratz, Harald; Wiekhorst, Frank; Warmuth, Carsten; Schnorr, Jörg; Genter, Gesche; Ebert, Monika; Mueller, Susanne; Schellenberger, Eyk

    2015-07-01

    To further optimize citrate-stabilized VSOPs (very small iron oxide particles, developed for MR angiography) for identification of atherosclerotic plaques, we modified their surface during synthesis using eight other acids for electrostatic stabilization. This approach preserves effective production for clinical application. Five particles were suitable to be investigated in targeting plaques of apoE(-/-) mice. Accumulation was evaluated by ex vivo MRI, TEM, and quantitatively by magnetic particle spectroscopy (MPS). Citric- (VSOP), etidronic-, tartaric-, and malic-acid-coated particles accumulated in atherosclerotic plaques with highest accumulation for VSOP (0.2‰ of injected dose). Targets were phagolysosomes of macrophages and of altered endothelial cells. In vivo MRI with VSOP allowed for definite plaque identification. Prussian blue staining revealed abundant endogenous iron in plaques, indistinguishable from particle iron. In apoE(-/-) mice, VSOPs are still the best anionic iron oxide particles for imaging atherosclerotic plaques. MPS allows for quantification of superparamagnetic nanoparticles in such small specimens. The presence of vulnerable plaques in arteries is important for the prediction of acute coronary events. VSOP (very small iron oxide particles, developed for MR angiography) have been shown to be very sensitive in identifying atherosclerotic plaques. The authors studied here further modification to the surface of VSOP during synthesis and compared their efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.

  17. Intravascular probe for detection of vulnerable plaque

    Science.gov (United States)

    Patt, Bradley E.; Iwanczyk, Jan S.; MacDonald, Lawrence R.; Yamaguchi, Yuko; Tull, Carolyn R.; Janecek, Martin; Hoffman, Edward J.; Strauss, H. William; Tsugita, Ross; Ghazarossian, Vartan

    2001-12-01

    Coronary angiography is unable to define the status of the atheroma, and only measures the luminal dimensions of the blood vessel, without providing information about plaque content. Up to 70% of heart attacks are caused by minimally obstructive vulnerable plaques, which are too small to be detected adequately by angiography. We have developed an intravascular imaging detector to identify vulnerable coronary artery plaques. The detector works by sensing beta or conversion electron radiotracer emissions from plaque-binding radiotracers. The device overcomes the technical constraints of size, sensitivity and conformance to the intravascular environment. The detector at the distal end of the catheter uses six 7mm long by 0.5mm diameter scintillation fibers coupled to 1.5m long plastic fibers. The fibers are offset from each other longitudinally by 6mm and arranged spirally around a guide wire in the catheter. At the proximal end of the catheter the optical fibers are coupled to an interface box with a snap on connector. The interface box contains a position sensitive photomultiplier tube (PSPMT) to decode the individual fibers. The whole detector assembly fits into an 8-French (2.7 mm in diameter) catheter. The PSPMT image is further decoded with software to give a linear image, the total instantaneous count rate and an audio output whose tone corresponds to the count rate. The device was tested with F-18 and Tl-204 sources. Spectrometric response, spatial resolution, sensitivity and beta to background ratio were measured. System resolution is 6 mm and the sensitivity is >500 cps / micrometers Ci when the source is 1 mm from the detector. The beta to background ratio was 11.2 for F-18 measured on a single fiber. The current device will lead to a system allowing imaging of labeled vulnerable plaque in coronary arteries. This type of signature is expected to enable targeted and cost effective therapies to prevent acute coronary artery diseases such as: unstable angina

  18. Folate receptor-β imaging using 99mTc-folate to explore distribution of polarized macrophage populations in human atherosclerotic plaque

    NARCIS (Netherlands)

    Jager, Nynke A.; Westra, Johanna; Golestani, Reza; van Dam, Gooitzen M.; Low, Philip S.; Tio, Rene A.; Slart, Riemer H. J. A.; Boersma, Hendrikus; Bijl, Marc; Zeebregts, Clark J.

    2014-01-01

    UNLABELLED: In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the pr

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arna van Engelen

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

  1. A role for archaeal organisms in development of atherosclerotic vulnerable plaques and myxoid matrices Um papel para organismos de arqueia no desenvolvimento de placas ateroscleróticas vulner��veis e matriz mixomatosa

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    Maria L Higuchi

    2006-10-01

    Full Text Available PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulnerable plaques, and possible associations with myxoid matrix, chlamydia, and mycoplasma bodies. METHODS: Twenty-nine tissue samples from 13 coronary artherectomies from large excentric ostial or bifurcational lesions were studied using optical and electron microscopy. Infectious agents compatible with archaea, chlamydia, and mycoplasma were semiquantified using electron micrographs and correlated with the amounts of fibromuscular tissue, myxoid matrix, and foam cells, as determined from semi-thin sections. Six of the cases were also submitted to polymerase chain reaction with archaeal primers. RESULTS: All 13 specimens showed archaeal-compatible structures and chlamydial and mycoplasmal bodies in at least 1 sample. There was a positive correlation between extent of the of myxoid matrix and archaeal bodies (r = 0.44, P = 0.02; between archaeal and mycoplasmal bodies (r = 0.41, P = 0.03, and between chlamydial bodies and foam cells (r = 0.42; P = 0.03. The PCR test was positive for archaeal DNA in 4 of the 6 fragments. DISCUSSION: DNA and forms suggestive of archaea are present in vulnerable plaques and may have a fundamental role in the proliferation of mycoplasma and chlamydia. This seems to be the first description of apparently pathogenic archaea in human internal organ lesions.PROPOSTA: Placas vulneráveis são caracterizadas por matriz mixomatosa, centro lipídico necrótico, espécies reativas de oxigênio e alto níveis de microorganismos. Micróbios aer

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Intravascular photoacoustic detection of vulnerable plaque based on constituent selected imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jian; Xing Da, E-mail: xingda@scnu.edu.cn [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631 (China)

    2011-01-01

    Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. Over decades, atherosclerosis is characterized by thickening of the walls of the arteries, only advanced atherosclerotic disease could be observed. Photoacoustic imaging is a hybrid imaging technique that combines the advantages of high spatial resolution of ultrasound with contrast of optical absorption. In this paper, we present an intravascular photoacoustic (IVPA) imaging system to characterize vulnerable plaques by using the optical absorption contrast between different constituents. Epidemiological studies have revealed several important plaque constituents associated with early atherosclerosis, such as macrophage, cholesterol, lipid, calcification, and so on. We chose a section of lipid rich atherosclerosis artery and a section of normal artery as the phantom. Two IVPA images of them are given to show the difference between sick and normal. As a new method of detecting vulnerable plaque, IVPA constituents imaging will provide more details for diagnosis that offer an enticing prospect in early detecting of atherosclerosis.

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

    Science.gov (United States)

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

    2015-02-01

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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    YAN Jun

    2013-10-01

    Full Text Available Carotid atherosclerosis is closely related with ischemic stroke occurrence, development and recurrence. This study aims to make an evaluation of the effects of rosuvastatin on inflammatory factors, serum lipid and carotid atherosclerotic plaque in patients with acute ischemic stroke. In this study, 98 patients with acute ischemic stroke and carotid atherosclerosis were given oral administration of rosuvastatin calcium (10 mg once every night, and the course of treatment was 6 months. After treatment, the changes of serum high-sensitivity C-reactive protein (hs-CRP, tumor necrosis factor-alpha (TNF-α and blood lipid were measured, as well as carotid atherosclerotic intima-media thickness (IMT and the calculation of carotid atherosclerotic plaque score. According to the examination results, after 6 months' treatment with rosuvastatin, serum hs-CRP, TNF-α, total cholesterol (TC, triglyceride (TG and low-density lipoprotein cholestrol (LDL-C decreased significantly (P < 0.01, for all, while high-density lipoprotein cholestrol (HDL-C increased significantly (P < 0.01; the total number of plaque reduced, while the number of stable plaque increased (P < 0.05; carotid artery IMT and carotid artery plaque score decreased significantly (P < 0.05. There were significant differences between before and after treatment. The results of this study show that rosuvastatin plays a role in anti-inflammation and alleviates the degree of carotid atherosclerotic plaque.

  10. Spectroscopy to improve identification of vulnerable plaques in cardiovascular disease.

    Science.gov (United States)

    Bruggink, Janneke L M; Meerwaldt, Robbert; van Dam, Gooitzen M; Lefrandt, Joop D; Slart, Riemer H J A; Tio, René A; Smit, Andries J; Zeebregts, Clark J

    2010-01-01

    Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.

  11. 前列腺素E1对兔动脉粥样硬化易损斑块内新生血管的影响%Effects of Prostaglanadin E1 on Angiogenesis in Atherosclerotic Vulnerable Plaques in Rabbits

    Institute of Scientific and Technical Information of China (English)

    郑雪; 白万军; 周聊生; 李宏建

    2012-01-01

    目的 建立兔动脉粥样硬化易损斑块模型,选择辛伐他汀为阳性对照药物,观察前列腺素E1对斑块易损指数及斑块内新生血管的影响.方法 将30只新西兰兔随机分为模型组、前列腺素E1组、辛伐他汀组,每组10只,建立易损斑块模型,并进行药物干预.腹主动脉切片进行形态学及斑块内出血观察;计算斑块易损指数;免疫组化观察斑块内相关因子表达;逆转录聚合酶链反应检测相关因子mRNA表达水平.结果 与模型组相比,前列腺素E1组斑块易损指数显著降低(1.23±0.23比2.84±0.59,P<0.05),血小板内皮细胞黏附分子1的表达明显减少(0.153±0.031比0.381±0.062,P<0.05),斑块内出血现象明显减轻;并且能够显著降低斑块内缺氧诱导因子1α、血管内皮生长因子蛋白表达(0.252±0.032比0.439±0.044,P<0.01;0.396±0.026比0.673±0.084,P<0.01)及mRNA水平(0.706±0.032比1.183±0.134,P<0.05;0.121±0.019比0.468±0.022,P<0.05);前列腺素E1组和辛伐他汀组斑块内缺氧诱导因子1α的蛋白表达及mRNA水平具有显著性差异(0.252±0.032比0.163±0.018,P <0.05;0.706±0.032比0.763±0.018,P<0.05).结论 前列腺素E1能够抑制斑块内新生血管的生成,具有稳定易损斑块的作用,其可能机制与辛伐他汀有所不同,是通过抑制斑块内缺氧诱导因子1α的激活进而下调血管内皮生长因子表达发挥作用.%Aim To establish the rabbit model of atherosclerotic vulnerable plaques, and study the effects of prostaglandin El on the angiogenesis which is induced by atherosclerosis. Methed 30 New Zealand white rabbits were randomly divided into 3 groups (model group, prostaglandin El group, and simvastatin group), each group has 10 rabbits. The rabbit model of atherosclerotic vulnerable plaques were established, and the rabbits were given drugs to affect the disease. The abdominal aorta were processed and examined by hematoxylin-eosin (HE) staining. The

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    Atherosclerosis is one of the main causes of death in developed countries. Atheroma plaque formation is promoted by the interaction between the cells conforming the arterial wall, smooth muscle cells, and endothelial cells, together with lipoproteins and inflammatory cells (mainly macrophages and T......-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...

  13. Stability Analysis of a Model of Atherosclerotic Plaque Growth

    Directory of Open Access Journals (Sweden)

    Sushruth Reddy

    2015-01-01

    Full Text Available Atherosclerosis, the formation of life-threatening plaques in blood vessels, is a form of cardiovascular disease. In this paper, we analyze a simplified model of plaque growth to derive physically meaningful results about the growth of plaques. In particular, the main results of this paper are two conditions, which express that the immune response increases as LDL cholesterol levels increase and that diffusion prevails over inflammation in a healthy artery.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    BACKGROUND: Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular......-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women...... with aortic calcifications compared to those without. CONCLUSIONS: Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution...

  15. Overexpression of Prolyl-4-Hydroxylase-α1 Stabilizes but Increases Shear Stress-Induced Atherosclerotic Plaque in Apolipoprotein E-Deficient Mice

    Science.gov (United States)

    Liu, Xin-xin; Li, Meng-meng; Zhang, Yu; Chen, Liang; Wang, Lin; Di, Ming-xue

    2016-01-01

    The rupture and erosion of atherosclerotic plaque can induce coronary thrombosis. Prolyl-4-hydroxylase (P4H) plays a central role in the synthesis of all known types of collagens, which are the most abundant constituent of the extracellular matrix in atherosclerotic plaque. The pathogenesis of atherosclerosis is thought to be in part caused by shear stress. In this study, we aimed to investigate a relationship between P4Hα1 and shear stress-induced atherosclerotic plaque. Carotid arteries of ApoE−/− mice were exposed to low and oscillatory shear stress conditions by the placement of a shear stress cast for 2 weeks; we divided 60 male ApoE−/− mice into three groups for treatments with saline (mock) (n = 20), empty lentivirus (lenti-EGFP) (n = 20), and lentivirus-P4Hα1 (lenti-P4Hα1) (n = 20). Our results reveal that after 2 weeks of lenti-P4Hα1 treatment both low and oscillatory shear stress-induced plaques increased collagen and the thickness of fibrous cap and decreased macrophage accumulation but no change in lipid accumulation. We also observed that overexpression of P4Ha1 increased plaque size. Our study suggests that P4Hα1 overexpression might be a potential therapeutic target in stabilizing vulnerable plaques.

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

    Directory of Open Access Journals (Sweden)

    Radak Đorđe

    2004-01-01

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

  17. Circulating CD36 and fractalkine levels are associated with vulnerable plaque progression in patients with unstable angina pectoris.

    Science.gov (United States)

    Li, Rui Jian; Yang, Ming; Li, Ji Fu; Xue, Li; Chen, Yu Guo; Chen, Wen Qiang

    2014-11-01

    The chemokine, fractalkine, independently enhances the vulnerability of coronary atherosclerotic plaques. The present study investigated the combined effects of CD36 and fractalkine on coronary plaque progression in patients with unstable angina pectoris. In the present study, 120 unstable angina pectoris patients undergoing coronary angiography and intravascular ultrasound were divided into two groups: an intermediate lesion group (lumen diameter stenosis 50-70%, 80 patients) and a severe lesion group (at least one lesion with lumen diameter stenosis > 70%, 40 patients). The control group consisted of 40 healthy age- and sex-matched subjects. Concentrations of CD36 and fractalkine were measured by enzyme-linked immunosorbent assay. Major adverse cardiovascular events were monitored over a 2-year follow up. Intravascular ultrasound showed that patients with severe lesions had more calcified and mixed plaques, and a larger plaque area and plaque burden than patients with intermediate lesions (P < 0.05-0.01). More patients with severe lesions underwent stent deployment (P < 0.05) than those with intermediate lesions. CD36 and fractalkine concentrations were significantly higher in the severe lesion patients (P < 0.05), and both had significant positive correlations (P < 0.05) with the plaque burden of atherosclerotic lesions. Using the matched nested case-control study, we found that CD36 and fractalkine levels were higher in patients with recurrent major adverse cardiovascular events than controls (P < 0.05). In conclusion, CD36 and fractalkine both promote, and might synergistically enhance, the progression of coronary atherosclerotic plaques.

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

    Science.gov (United States)

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

    2016-01-01

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

  19. 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...

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

    Directory of Open Access Journals (Sweden)

    Omid MASOUMI

    2015-10-01

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

  1. A Meta Analysis and Hierarchical Classification of HU-Based Atherosclerotic Plaque Characterization Criteria

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; van Ooijen, Peter M. A.; Jansen-van der Weide, Marijke C.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs

    2013-01-01

    Background: Many computed tomography (CT) studies have reported that lipid-rich, presumably rupture-prone atherosclerotic plaques can be characterized according to their Hounsfield Unit (HU) value. However, the published HU-based characterization criteria vary considerably. The present study aims to

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2008-02-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-11-01

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

  6. In vitro atherosclerotic plaque and calcium quantitation by intravascular ultrasound and electron-beam computed tomography.

    Science.gov (United States)

    Gutfinger, D E; Leung, C Y; Hiro, T; Maheswaran, B; Nakamura, S; Detrano, R; Kang, X; Tang, W; Tobis, J M

    1996-05-01

    The purpose of this investigation was to compare the accuracy of intravascular ultrasound (IVUS) and electron-beam computed tomography (EBCT) in quantitating human atherosclerotic plaque and calcium. In experiment 1, 12 human atherosclerotic arterial segments were obtained at autopsy and imaged by using IVUS and EBCT. The plaque from each arterial segment was dissected and a volume measurement of the dissected plaque was obtained by water displacement. The plaque from each arterial segment was ashed at 700 degrees F, and the weight of the remaining ashes was used as an estimate of the calcium mass. In experiment II, 11 calcified arterial segments were obtained at autopsy and imaged by using IVUS at one site along the artery. A corresponding histologic cross section stained with Masson's trichrome was prepared. In experiment I, the mean plaque volume measured by water displacement was 165.3 +/- 118.4 microliters. The mean plaque volume calculated by IVUS was 166.1 +/- 114.4 microliters and correlated closely with that by water displacement (r = 0.98, p volume by IVUS was 18.6 +/- 11.2 microliters and correlated linearly with the calcium mass by ashing (r = 0.87, p volume as well as the cross-sectional area and volume of intralesional calcium, especially if the calcium is localized at the base of the plaque. IVUS underestimates the amount of calcium present because of signal drop-off when the calcium is too thick for the ultrasound to completely penetrate. In comparison, EBCT accurately quantitates calcium mass regardless of the intralesional calcium morphologic characteristics; however, EBCT does not accurately quantitate plaque volume and will miss noncalcified atherosclerotic lesions.

  7. 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.

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

    Science.gov (United States)

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

    2010-10-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Larsen Lise

    2010-04-01

    Full Text Available Abstract Background Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture. The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular matrix (ECM of atherosclerotic plaques by cathepsin K mediated processes. Methods We 1 cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I 2 investigated the presence of CTX-I in human coronary arteries and 3 finally investigated the clinical potential by measuring circulating CTX-I in women with and without radiographic evidence of aortic calcified atherosclerosis. Results Immune-histochemistry of early and advanced lesions of coronary arteries demonstrated co-localization of Cathepsin-K and CTX-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women with aortic calcifications compared to those without. Conclusions Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution of CTX-I from osteoclastic bone resorption which involves Cathepsin-K. The human macrophage model system may be used to identify important pathway leading to excessive proteolytic plaque remodeling and plaque rupture.

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

    Science.gov (United States)

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

    1996-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Ian C Campbell

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

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

    Science.gov (United States)

    Kim, Taehong; Ley, Obdulia

    2008-06-01

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

  14. The usefulness of optical analyses for detecting vulnerable plaques using rabbit models

    Science.gov (United States)

    Nakai, Kanji; Ishihara, Miya; Kawauchi, Satoko; Shiomi, Masashi; Kikuchi, Makoto; Kaji, Tatsumi

    2011-03-01

    Purpose: Carotid artery stenting (CAS) has become a widely used option for treatment of carotid stenosis. Although technical improvements have led to a decrease in complications related to CAS, distal embolism continues to be a problem. The purpose of this research was to investigate the usefulness of optical methods (Time-Resolved Laser- Induced Fluorescence Spectroscopy [TR-LIFS] and reflection spectroscopy [RS] as diagnostic tools for assessment of vulnerable atherosclerotic lesions, using rabbit models of vulnerable plaque. Materials & Methods: Male Japanese white rabbits were divided into a high cholesterol diet group and a normal diet group. In addition, we used a Watanabe heritable hyperlipidemic (WHHL) rabbit, because we confirmed the reliability of our animal model for this study. Experiment 1: TR-LIFS. Fluorescence was induced using the third harmonic wave of a Q switch Nd:YAG laser. The TR-LIFS was performed using a photonic multi-channel analyzer with ICCD (wavelength range, 200 - 860 nm). Experiment 2: RS. Refection spectra in the wavelength range of 900 to 1700 nm were acquired using a spectrometer. Results: In the TR-LIFS, the wavelength at the peak was longer by plaque formation. The TR-LIFS method revealed a difference in peak levels between a normal aorta and a lipid-rich aorta. The RS method showed increased absorption from 1450 to 1500 nm for lipid-rich plaques. We observed absorption around 1200 nm due to lipid only in the WHHL group. Conclusion: These methods using optical analysis might be useful for diagnosis of vulnerable plaques. Keywords: Carotid artery stenting, vulnerable plaque, Time-Resolved Laser-Induced Fluorescence

  15. Motion compensation method using dynamic programming for quantification of neovascularization in carotid atherosclerotic plaques with contrast enhanced ultrasound (CEUS)

    Science.gov (United States)

    Akkus, Zeynettin; Hoogi, Assaf; Renaud, Guillaume; ten Kate, Gerrit L.; van den Oord, Stijn C. H.; Schinkel, Arend F. L.; de Jong, Nico; van der Steen, Antonius F. W.; Bosch, Johan G.

    2012-03-01

    Intraplaque neovascularization (IPN) has been linked with progressive atherosclerotic disease and plaque instability in several studies. Quantification of IPN may allow early detection of vulnerable plaques. A dedicated motion compensation method with normalized-cross-correlation (NCC) block matching combined with multidimensional (2D+time) dynamic programming (MDP) was developed for quantification of IPN in small plaques (images of carotid arteries were acquired by a Philips iU22 system with a L9-3 linear array probe. The motion pattern for the plaque region was obtained from the Bmode images with MDP. MDP results were evaluated in-vitro by a phantom and in-vivo by comparing to manual tracking of three experts for multibeat-image-sequences (MIS) of 11 plaques. In the in-vivo images, the absolute error was 72+/-55μm (mean+/-SD) for X (longitudinal) and 34+/-23μm for Y (radial). The method's success rate was visually assessed on 67 MIS. The tracking was considered failed if it deviated >2 pixels (~200μm) from true motion in any frame. Tracking was scored as fully successful in 63 MIS (94%) for MDP vs. 52(78%) for FT. The range of displacement over these 63 was 1045+/-471μm (X) and 395+/-216μm (Y). The tracking sporadically failed in 4 MIS (6%) due to poor image quality, jugular vein proximity and out-of-plane motion. Motion compensation showed improved lumen-plaque contrast separation. In conclusion, the proposed method is sufficiently accurate and successful for in vivo application.

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

    Science.gov (United States)

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

    2016-02-12

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

  17. 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.

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

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    topics have been investigated: an ultrasound pulse-echo simulation tool and a new compound imaging technique for improving visualization of atherosclerotic disease.A tool for simulation of the received electrical signal in a pulse-echo ultrasound system, due to a reflector surface of arbitrary geometry......, has been developed. The method is denoted the Diffraction Response Interpolation Method (DRIM) and is based on the pulse-echo diffraction impulse response method. The DRIM is a computationally efficient tool for calculating the integral of the spatially varying pulse-echo diffraction impulse response...... definition of the interfaces in the cases where one or more of the beams had near-normal incidence on the interface, i.e. an improved visualization over an angular range of interface orientations roughly corresponding to the range of beam angles used. The speckle statistics and the speckle reduction have...

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

    Directory of Open Access Journals (Sweden)

    Paul F Bradfield

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.

    Directory of Open Access Journals (Sweden)

    Stefan Chłopicki

    2008-06-01

    Full Text Available This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/- mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA, macrophages (rat anti-CD68 and T lymphocytes (rabbit anti-CD3. Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. Detection of vulnerable plaques rather than the culprit lesions in patients with acute coronary syndrome using virtual histology intravascular ultrasound imaging

    Institute of Scientific and Technical Information of China (English)

    QIAN Ju-ying

    2009-01-01

    @@ Pathology and postmortem studies have reported that the most important mechanism of acute coronary syndrome (ACS) is the rupture of a vulnerable plaque and subsequent thrombus formation. Such events commonly arise from the non-flow limiting atherosclerotic lesions which are prone to rupture. Thin-cap fibroatheromas (TCFA) are the most common type of vulnerable plaque. As the widely used technique for the detection of coronary arterial diseases, coronary angiography has intrinsic limitations since it only portrays the contrast agent-filled contour of the lumen and provides little information on the vessel wall and even less the characteristics of the plaques.

  4. The association between Chlamydia pneumoniae DNA in atherosclerotic plaque and major risk factors in patients undergoing coronary artery bypass grafting

    NARCIS (Netherlands)

    Hedayat, Daryoosh Kamal; Jebeli, Mohammad; Mandegar, Mohammad Hossein; Bagheri, Jamshid; Nabavi, Seyed Abbas; Eghtesadi-Araghi, Payam; Mohammadzadeh, Robabeh; Darehzereshki, Ali; Chitsaz, Sam; Abbasi, Ali

    2009-01-01

    Background and aim: This study was conducted to investigate the prevalence of Chlamydia pneumoniae pathogen inside the atherosclerotic plaque of patients undergoing CABG by using PCR assay and to determine whether there is any association between the presence of bacteria in atherosclerotic lesions a

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

    Science.gov (United States)

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

    2017-01-01

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

  6. Salidroside Decreases Atherosclerotic Plaque Formation in Low-Density Lipoprotein Receptor-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Bu-Chun Zhang

    2012-01-01

    Full Text Available Salidroside is isolated from Rhodiola rosea and is one of the main active components in Rhodiola species. The present study was designed to evaluate the effects of Salidroside on atherosclerotic plaque formation in high-fat diet-(HFD- fed female LDL receptor knockout (LDLr-/- mice. LDLr-/- mice fed an atherogenic HFD for 12 weeks were divided into two groups. One group was administered Salidroside (50 mg/kg/oral gavage daily for 8 weeks, while the control group was administered saline. Salidroside treatment reduced serum lipids levels and the plaque area through the arch to the abdominal aorta. Furthermore, Salidroside improved macrophage content and enhanced collagen and smooth muscle cells contents in the aortic sinus. These changes were associated with reduced MCP-1, VCAM-1, and VCAM-1 protein expression in atherosclerotic aortas. All these results suggest that Salidroside decreases atherosclerotic plaques formation via effects on lipid lowering and anti-inflammation in HFD-fed LDLr−/− mice.

  7. Lumen irregularity dominates the relationship between mechanical stress condition, fibrous-cap thickness, and lumen curvature in carotid atherosclerotic plaque.

    Science.gov (United States)

    Teng, Zhongzhao; Sadat, Umar; Ji, Guangyu; Zhu, Chengcheng; Young, Victoria E; Graves, Martin J; Gillard, Jonathan H

    2011-03-01

    High mechanical stress condition over the fibrous cap (FC) has been widely accepted as a contributor to plaque rupture. The relationships between the stress, lumen curvature, and FC thickness have not been explored in detail. In this study, we investigate lumen irregularity-dependent relationships between mechanical stress conditions, local FC thickness (LT(FC)), and lumen curvature (LC(lumen)). Magnetic resonance imaging slices of carotid plaque from 100 patients with delineated atherosclerotic components were used. Two-dimensional structure-only finite element simulations were performed for the mechanical analysis, and maximum principal stress (stress-P₁) at all integral nodes along the lumen was obtained. LT(FC) and LC(lumen) were computed using the segmented contour. The lumen irregularity (L-δir) was defined as the difference between the largest and the smallest lumen curvature. The results indicated that the relationship between stress-P₁, LT(FC), and LC(lumen) is largely dependent on L-δir. When L-δir ≥ .31 (irregular lumen), stress-P₁ strongly correlated with lumen curvature and had a weak/no correlation with local FC thickness, and in 73.4% of magnetic resonance (MR) slices, the critical stress (maximum of stress-P₁ over the diseased region) was found at the site where the lumen curvature was large. When L-δir ≤ 0.28 (relatively round lumen), stress-P₁ showed a strong correlation with local FC thickness but weak/no correlation with lumen curvature, and in 71.7% of MR slices, the critical stress was located at the site of minimum FC thickness. Using lumen irregularity as a method of identifying vulnerable plaque sites by referring to the lumen shape is a novel and simple method, which can be used for mechanics-based plaque vulnerability assessment.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-15

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

  10. 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...

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  12. 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

    Full Text Available In most patients with type 2 diabetes, along with the presence of disturbances of glycemic control, there are disturbances of lipid metabolism and elevated blood pressure, which are strong risk factors for the development of late, especially macrovascular complications and whose base is the vulnerable atherosclerotic plaque. This study included a total of 101 individuals (51 patients suffering from diabetes mellitus type 2-DMT2 and 50 healthy subjects. Distribution of respondents according to the presence of hyperlipoproteinaemia, vulnerable and invulnerable atherosclerotic plaque was done. The data were analyzed by appropriate statistical tests. Hyperlipidaemia was more prevalent in patients with DMT2 than in the control ones (p<0.05. Cholesterol levels were significantly higher (p<0.05 in subjects with DMT2 (5.74±2.69 vs. 4.82±1.11mmol/L as well as triglycerides (1.94±2.2 compared to 1.6±1.14mmol/L (p<0.001. Mean values of glucose in the group of subjects with diabetes mellitus type 2 (10.54±3.75mmol/L and in the control group (4.53±2.14mmol/L were significantly different (p<0.001. Glycosylated hemoglobin HbA1c was significantly higher in patients with DMT2 (9.30±2.26% than control group (4.98±0.05%. Mean values of both systolic and diastolic blood pressure were significantly higher in subjects with diabetes mellitus type 2 (149.55±29.27mmHg and 87.92±17.58mmHg compared to those in the control group (mean systolic blood pressure of 128.32±25.77 and mean diastolic blood pressure 79.11±9.51mmHg. Plaque was found in 100% of diabetic patients, as opposed to 28.12% of patients in the control group. Vulnerable plaque was found in 47.06% of patients in the group with type 2 diabetes and 6.25% in the control group. Analysis with the Mann-Whitney-test shows that the incidence of plaque and vulnerable plaque was significantly higher in DMT2 patients (p<0.001. Hyperlipidaemia, hypertension and type 2 diabetes mellitus are significantly

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

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

  14. Local axial compressive mechanical properties of human carotid atherosclerotic plaques-characterisation by indentation test and inverse finite element analysis.

    Science.gov (United States)

    Chai, Chen-Ket; Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H; Oomens, Cees W J; van Sambeek, Marc R H M; van der Lugt, Aad; Baaijens, Frank P T

    2013-06-21

    The fibrous cap of an atherosclerotic plaque may be prone to rupture if the occurring stresses exceed the strength of the cap. Rupture can cause acute thrombosis and subsequent ischaemic stroke or myocardial infarction. A reliable prediction of the rupture probability is essential for the appropriate treatment of atherosclerosis. Biomechanical models, which compute stresses and strain, are promising to provide a more reliable rupture risk prediction. However, these models require knowledge of the local biomechanical properties of atherosclerotic plaque tissue. For this purpose, we examined human carotid plaques using indentation experiments. The test set-up was mounted on an inverted confocal microscope to visualise the collagen fibre structure during the tests. By using an inverse finite element (FE) approach, and assuming isotropic neo-Hookean behaviour, the corresponding Young's moduli were found in the range from 6 to 891kPa (median 30kPa). The results correspond to the values obtained by other research groups who analysed the compressive Young's modulus of atherosclerotic plaques. Collagen rich locations showed to be stiffer than collagen poor locations. No significant differences were found between the Young's moduli of structured and unstructured collagen architectures as specified from confocal collagen data. Insignificant differences between the middle of the fibrous cap, the shoulder regions, and remaining plaque tissue locations indicate that axial, compressive mechanical properties of atherosclerotic plaques are independent of location within the plaque. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. 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.

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

    Science.gov (United States)

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

    2007-01-01

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

  17. Molecular imaging of vulnerable atherosclerosis. Preclinical and clinical evaluation of nuclear tracers; Imagerie moleculaire de la plaque d'atherome vulnerable. Evaluation preclinique et clinique de traceurs radioactifs

    Energy Technology Data Exchange (ETDEWEB)

    Broisat, A.; Riou, L.M.; Dimastromatteo, J.; Pons, G.; Fagret, D.; Ghezzi, C. [Inserm U877, radiopharmaceutiques biocliniques, 38 - Grenoble (France); Grenoble Univ., 38 (France); Dimastromatteo, J. [ERAS Labo, 38 - Saint-Nazaire-les-Eymes (France)

    2009-02-15

    Atherosclerotic cardiovascular diseases (C.V.D.) are the leading cause of mortality worldwide, accounting for greater than 19.106 deaths annually. Despite major advances in the treatment of C.V.D., a high proportion of C.V.D. victims die suddenly while being apparently healthy, the great majority of these accidents being due to the rupture or erosion of a vulnerable coronary atherosclerotic plaque. Indeed, an acute heart attack is the first symptom of atherosclerosis in as much as 50% of individuals with severe disease. A non-invasive imaging methodology allowing the early detection of vulnerable atherosclerosis in selected individuals prior to the occurrence of any symptom would therefore be of great public health benefit. Nuclear imaging could potentially allow the identification of vulnerable patients by non-invasive scintigraphic imaging following administration of a radiolabeled tracer. The development of radiolabeled probes that specifically bind to and allow the in vivo imaging of vulnerable atherosclerotic plaques is therefore the subject of intense ongoing experimental and clinical research. Radiotracers targeted at the inflammatory process seem particularly relevant and promising. Recently, macrophage targeting allowed the experimental in vivo detection of atherosclerosis using either SPECT or PET imaging. A few tracers have also been evaluated clinically. Targeting of apoptosis and macrophage metabolism both allowed the imaging of vulnerable atherosclerotic plaques in the carotid vessels of patients. However, nuclear imaging of vulnerable plaques at the level of the coronary arteries remains a challenging issue because of the small size of atherosclerotic lesions and of their vicinity with blood and the circulating tracer activity. (authors)

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

    Institute of Scientific and Technical Information of China (English)

    CAO Wei; ZHANG Yongxue; AN Rui

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-19

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

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

    Directory of Open Access Journals (Sweden)

    Dheeraj eKhurana

    2013-04-01

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

  1. Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques

    NARCIS (Netherlands)

    Razansky, Daniel; Harlaar, Niels J.; Hillebrands, Jan Luuk; Taruttis, Adrian; Herzog, Eva; Zeebregts, Clark J.; van Dam, Gooitzen M.; Ntziachristos, Vasilis

    Elevated expression of cathepsins, integrins and matrix metalloproteinases (MMPs) is typically associated with atherosclerotic plaque instability. While fluorescent tagging of such molecules has been amply demonstrated, no imaging method was so far shown capable of resolving these

  2. 3D reconstruction of carotid atherosclerotic plaque: comparison between spatial compound ultrasound models and anatomical models

    DEFF Research Database (Denmark)

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

    2007-01-01

    This study deals with the creation of 3D models that can work as a tool for discriminating between tissue and background in the development of tissue classification methods. Ten formalin-fixed atherosclerotic carotid plaques removed by endarterectomy were scanned with 3D multi-angle spatial...... compound ultrasound (US) and subsequently sliced and photographed to produce a 3D anatomical data set. Outlines in the ultrasound data were found by means of active contours and combined into 10 3D ultrasound models. The plaque regions of the anatomical photographs were outlined manually and then combined...... into 10 3D anatomical models. The volumes of the anatomical models correlated with the volume found by a water displacement method (r = 0.95), except for an offset. The models were compared in three ways. Visual inspection showed quite good agreement between the models. The volumes of the ultrasound...

  3. Relation of microchannel structure identified by optical coherence tomography to plaque vulnerability in patients with coronary artery disease.

    Science.gov (United States)

    Kitabata, Hironori; Tanaka, Atsushi; Kubo, Takashi; Takarada, Shigeho; Kashiwagi, Manabu; Tsujioka, Hiroto; Ikejima, Hideyuki; Kuroi, Akio; Kataiwa, Hideaki; Ishibashi, Kohei; Komukai, Kenichi; Tanimoto, Takashi; Ino, Yasushi; Hirata, Kumiko; Nakamura, Nobuo; Mizukoshi, Masato; Imanishi, Toshio; Akasaka, Takashi

    2010-06-15

    Increased neovascularization in atherosclerotic plaques is associated with plaque vulnerability. The high resolution of optical coherence tomography (OCT) might provide a chance to directly visualize plaque neovascularization in vivo. The aim of the present study was to investigate the relation between microchannels in culprit plaques identified by OCT and plaque vulnerability in patients with coronary artery disease. A total of 63 consecutive patients with coronary artery disease who had undergone both OCT and intravascular ultrasound before any interventions to examine culprit lesion morphologies were enrolled. Microchannel was defined as a no-signal tubuloluminal structure on the cross-sectional optical coherence tomographic image. Microchannels were found in 24 (38%) of the 63 patients. The patients were divided into 2 groups according to the presence or absence of microchannels. The frequency of plaque rupture tended to be greater in the microchannel group (50% vs 28%, p = 0.11). The thickness of the fibrous cap (median 60 vs 100 microm, p = 0.001) was significantly less in the patients with microchannels, and significant differences were found in the frequency of thin-cap fibroatheroma (54% vs 21%, p = 0.012) and positive remodeling (67% vs 36%, p = 0.02) between the 2 groups. The high-sensitivity C-reactive protein levels in the microchannel group was significantly greater than those in the no-microchannel group (median 0.27 vs 0.13 mg/dl, p = 0.015). Moreover, increased microchannel counts were associated with greater high-sensitivity C-reactive protein levels (p = 0.01). In conclusion, a significant relation was found between the presence of microchannels in plaques identified by OCT and plaque vulnerability in patients with coronary artery disease.

  4. The protein and lipid composition of arterial elastin and its relationship to lipid accumulation in the atherosclerotic plaque.

    Science.gov (United States)

    Kramsch, D M; Franzblau, C; Hollander, W

    1971-08-01

    Elastin preparations from intimal layers and the media of normal and atherosclerotic human aortae were analyzed for protein and lipid content. In atherosclerotic aortae, elastin from plaques was compared with elastin from adjacent normal appearing areas of the same aorta. Arterial elastin purified by alkaline extraction appeared to be a protein-lipid complex containing free and ester cholesterol, phospholipids, and triglycerides. The lipid component of normal arterial elastin was small (1-2%). With increasing severity of atherosclerosis, there was a progressive accumulation of lipid in intimal elastin from plaques, reaching a mean lipid content of 37% in severe plaques. The increase in the lipid content of plaque elastic preparations was mainly due to large increases in cholesterol, over 80% of which was cholesteryl ester. This deposition of cholesterol in plaque elastin accounted for 20-34% of the total cholesterol content of the plaque. The increased lipid deposition in plaque elastin was associated with alterations in the amino acid composition of plaque elastin. In elastin from plaque intima, the following polar amino acids were increased significantly: aspartic acid, threonine, serine, glutamic acid, lysine, histidine, and arginine; whereas, cross-linking amino acids: desmosine, isodesmosine, and lysinonorleucine were decreased significantly. The amino acid and lipid composition of elastin from normal appearing aortic areas was comparable to that of normal arterial elastin except for intimal elastin directly adjacent to and medial elastin directly below the most severe plaques.The data indicate that the focal lipid deposition in early atherosclerotic plaques is due to a large extent to lipid accumulations in altered elastin protein of localized intimal areas. Continued lipid deposition in altered elastin appears to contribute substantially to the progressive lipid accumulation in the plaque. The study suggests that elastin of intimal elastic membranes may play

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhe Wang

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

  9. Identifying Vulnerable Plaques with Acoustic Radiation Force Impulse Imaging

    Science.gov (United States)

    Doherty, Joshua Ryan

    The rupture of arterial plaques is the most common cause of ischemic complications including stroke, the fourth leading cause of death and number one cause of long term disability in the United States. Unfortunately, because conventional diagnostic tools fail to identify plaques that confer the highest risk, often a disabling stroke and/or sudden death is the first sign of disease. A diagnostic method capable of characterizing plaque vulnerability would likely enhance the predictive ability and ultimately the treatment of stroke before the onset of clinical events. This dissertation evaluates the hypothesis that Acoustic Radiation Force Impulse (ARFI) imaging can noninvasively identify lipid regions, that have been shown to increase a plaque's propensity to rupture, within carotid artery plaques in vivo. The work detailed herein describes development efforts and results from simulations and experiments that were performed to evaluate this hypothesis. To first demonstrate feasibility and evaluate potential safety concerns, finite- element method simulations are used to model the response of carotid artery plaques to an acoustic radiation force excitation. Lipid pool visualization is shown to vary as a function of lipid pool geometry and stiffness. A comparison of the resulting Von Mises stresses indicates that stresses induced by an ARFI excitation are three orders of magnitude lower than those induced by blood pressure. This thesis also presents the development of a novel pulse inversion harmonic tracking method to reduce clutter-imposed errors in ultrasound-based tissue displacement estimates. This method is validated in phantoms and was found to reduce bias and jitter displacement errors for a marked improvement in image quality in vivo. Lastly, this dissertation presents results from a preliminary in vivo study that compares ARFI imaging derived plaque stiffness with spatially registered composition determined by a Magnetic Resonance Imaging (MRI) gold standard

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

    Institute of Scientific and Technical Information of China (English)

    霍煜

    2014-01-01

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

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

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    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.

  12. Effects of insulin sensitizers on plaque vulnerability associated with elevated lipid content in atheroma in ApoE-knockout mice.

    Science.gov (United States)

    Cefalu, W T; Wang, Z Q; Schneider, D J; Absher, P M; Baldor, L C; Taatjes, D J; Sobel, B E

    2004-03-01

    Acute coronary syndromes are generally precipitated by rupture of lipid-laden, relatively acellular, vulnerable atherosclerotic plaques with thin fibrous caps. We investigated whether a high-fat diet alters insulin sensitivity and whether insulin sensitizers (troglitazone and rosiglitazone) alter the composition of otherwise lipidladen atherosclerotic plaques in mice deficient in apolipoprotein E (ApoE). ApoE-knockout mice were fed a high-fat (n=30) or standard chow (n=10) diet for two weeks. Thereafter, those fed the high-fat diet were treated with troglitazone (n=10), rosiglitazone (n=10) or no drug (n=10) for 16 weeks beginning at 8 weeks of age. Carbohydrate metabolism was assessed with intraperitoneal glucose tolerance tests and insulin tolerance tests. Plaque composition was characterised with confocal laser scanning microscopy. The high-fat diet induced insulin resistance in the absence of weight gain. Compared with control animals on the high-fat diet, animals given troglitazone (400 mg/kg/day) or rosiglitazone (4 mg/kg/day) had significantly less area under the curve (AUC) for insulin ( p<0.05) and glucose disposal ( p<0.05). Despite significant increases in insulin sensitivity with drug treatment, no change in HDL-cholesterol and triglyceride levels, nor reduction in atheroma size or lipid content was noted. Thus, improvement in insulin resistance induced by a high-fat diet in this animal model of vasculopathy did not alter plaque composition.

  13. 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

  14. Assessment of plaque vulnerability in atherosclerosis via intravascular photoacoustic imaging of targeted liposomal ICG J-aggregates (Conference Presentation)

    Science.gov (United States)

    Harris, Justin T.; Dumani, Diego S.; Cook, Jason R.; Sokolov, Konstantin V.; Emelianov, Stanislav Y.; Homan, Kimberly A.

    2017-03-01

    While molecular and cellular imaging can be used to visualize the conventional morphology characteristics of vulnerable plaques, there is a need to monitor other physiological factors correlated with high rupture rates; a high M1 activated macrophage concentration is one such indicator of high plaque vulnerability. Here, we present a molecularly targeted contrast agent for intravascular photoacoustic (IVPA) imaging consisting of liposomes loaded with indocyanine green (ICG) J-aggregates with high absorption at 890 nm, allowing for imaging in the presence of blood. This "Lipo-ICG" was targeted to a biomarker of M1 activated macrophages in vulnerable plaques: folate receptor beta (FRβ). The targeted liposomes accumulate in plaques through areas of endothelial dysfunction, while the liposome encapsulation prevents nonspecific interaction with lipids and endothelium. Lipo-ICG specifically interacts with M1 activated macrophages, causing a spectral shift and change in the 890/780 nm photoacoustic intensity ratio upon breakdown of J-aggregates. This sensing mechanism enables assessment of the M1 activated macrophage concentration, providing a measure of plaque vulnerability. In a pilot in vivo study utilizing ApoE deficient mouse models of atherosclerosis, diseased mice showed increased uptake of FRβ targeted Lipo-ICG in the heart and arteries vs. normal mice. Likewise, targeted Lipo-ICG showed increased uptake vs. two non-targeted controls. Thus, we successfully synthesized a contrast agent to detect M1 activated macrophages in high risk atherosclerotic plaques and exhibited targeting both in vitro and in vivo. This biocompatible agent could enable M1 macrophage detection, allowing better clinical decision making in treatment of atherosclerosis.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  17. 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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Chen Zhang

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

  20. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  2. 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.

  3. Rationale, Design, and Methodological Aspects of the BUDAPEST-GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions).

    Science.gov (United States)

    Maurovich-Horvat, Pál; Tárnoki, Dávid L; Tárnoki, Ádám D; Horváth, Tamás; Jermendy, Ádám L; Kolossváry, Márton; Szilveszter, Bálint; Voros, Viktor; Kovács, Attila; Molnár, Andrea Á; Littvay, Levente; Lamb, Hildo J; Voros, Szilard; Jermendy, György; Merkely, Béla

    2015-12-01

    The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST-GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single-center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same-sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non-contrast-enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non-contrast-enhanced image slice was acquired at the level of L3-L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3-dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per-patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST-GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders. © 2015 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

  7. 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.

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

    Science.gov (United States)

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

    2011-09-01

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

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

    Science.gov (United States)

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

    2013-01-01

    Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences (p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques (p = 5.4 × 10−7). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold (p = 0.0086) and five-fold (p = 0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential. PMID:23122912

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

    OpenAIRE

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Filippo Canducci

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Qing Sun

    2014-07-01

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

  15. Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy

    Science.gov (United States)

    Haka, Abigail S.; Kramer, John R.; Dasari, Ramachandra R.; Fitzmaurice, Maryann

    2011-01-01

    Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ∼40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque. PMID:21280898

  16. 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.

  17. 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

    improvement of 6.4%; P = 0.025), or from high intermediate to high FRS risk (net reclassification improvement 8.8%; P = 0.002). Assuming primary prevention could reduce the relative cardiovascular risk by 24-27%, on the basis of actual levels of blood pressure and cholesterol, one composite endpoint could...... risk patients and high-intermediate FRS risk patients with high risk (P = 0.04 and P = 0.001, respectively), whereas elevated carotid-femoral pulse wave velocity did not. Elevated UACR or presence of atherosclerotic plaques reclassified patients from moderate to high SCORE risk [net reclassification...... be avoided by giving primary prevention to 19 or 24 reclassified patients found by screening 52 or 104 patients with high-intermediate FRS or moderate SCORE risk, respectively. CONCLUSION: Elevated UACR and presence of atherosclerotic plaques could in a potentially cost-effective manner identify patients...

  18. Scintillating balloon-enabled fiber-optic system for radionuclide imaging of atherosclerotic plaques.

    Science.gov (United States)

    Zaman, Raiyan T; Kosuge, Hisanori; Carpenter, Colin; Sun, Conroy; McConnell, Michael V; Xing, Lei

    2015-05-01

    scintillating crystal to the balloon: 1.65 × 10(2) ± 4.07 × 10(1) vs. 4.44 × 10(1) ± 2.17 × 10(0) (photon counts), P = 0.005. Both external optical imaging and autoradiography confirmed the high signal from the (18)F-FDG in carotid plaques versus controls. This SBRI system provides high-resolution and sensitive detection of (18)F-FDG uptake by murine atherosclerotic plaques. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  19. A negative correlation between human carotid atherosclerotic plaque progression and plaque wall stress: in vivo MRI-based 2D/3D FSI models.

    Science.gov (United States)

    Tang, Dalin; Yang, Chun; Mondal, Sayan; Liu, Fei; Canton, Gador; Hatsukami, Thomas S; Yuan, Chun

    2008-01-01

    It is well accepted that atherosclerosis initiation and progression correlate positively with low and oscillating flow wall shear stresses (FSS). However, this mechanism cannot explain why advanced plaques continue to grow under elevated FSS conditions. In vivo magnetic resonance imaging (MRI)-based 2D/3D multi-component models with fluid-structure interactions (FSI, 3D only) for human carotid atherosclerotic plaques were introduced to quantify correlations between plaque progression measured by wall thickness increase (WTI) and plaque wall (structure) stress (PWS) conditions. A histologically validated multi-contrast MRI protocol was used to acquire multi-year in vivo MRI images. Our results using 2D models (200-700 data points/patient) indicated that 18 out of 21 patients studied showed significant negative correlation between WTI and PWS at time 2 (T2). The 95% confidence interval for the Pearson correlation coefficient is (-0.443,-0.246), p<0.0001. Our 3D FSI model supported the 2D correlation results and further indicated that combining both plaque structure stress and flow shear stress gave better approximation results (PWS, T2: R(2)=0.279; FSS, T1: R(2)=0.276; combining both: R(2)=0.637). These pilot studies suggest that both lower PWS and lower FSS may contribute to continued plaque progression and should be taken into consideration in future investigations of diseases related to atherosclerosis.

  20. Topographic association of angioscopic yellow plaques with coronary atherosclerotic plaque: assessment with quantitative colorimetry in human coronary artery autopsy specimens.

    Science.gov (United States)

    Ishibashi, Fumiyuki; Lisauskas, Jennifer B; Kawamura, Akio; Waxman, Sergio

    2008-01-01

    Yellow plaques seen during coronary angioscopy are thought to be the surrogates for superficial intimal lipids in coronary plaque. Given diffuse and heterogeneous nature of atherosclerosis, yellow plaques in coronaries may be seen as several yellow spots on diffuse coronary plaque. We examined the topographic association of yellow plaques with coronary plaque. In 40 non-severely stenotic ex-vivo coronary segments (average length: 52.2 +/- 3.1 mm), yellow plaques were examined by angioscopy with quantitative colorimetry. The segments were cut perpendicular to the long axis of the vessel at 2 mm intervals, and 1045 slides with 5 microm thick tissue for whole segments were prepared. To construct the plaque surface, each tissue slice was considered to be representative of the adjacent 2 mm. The circumference of the lumen and the lumen border of plaque were measured in each slide, and the plaque surface region was constructed. Coronary plaque was in 37 (93%) of 40 segments, and consisted of a single mass [39.9 +/- 3.9 (0-100) mm, 311.3 +/- 47.4 (0.0-1336.2) mm2]. In 30 (75%) segments, multiple (2-9) yellow plaques were detected on a mass of coronary plaque. The number of yellow plaques correlated positively with coronary plaque surface area (r = 0.77, P colorimetry, some of them are associated with lipid cores underneath thin fibrous caps, may be used to assess the extent of coronary plaque. Further research using angioscopy could be of value to study the association of high-risk coronaries with acute coronary syndromes.

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

    Science.gov (United States)

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

    2007-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Morteza Izadi

    2013-12-01

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

  3. Copper and zinc concentrations in atherosclerotic plaque and serum in relation to lipid metabolism in patients with carotid atherosclerosis

    Directory of Open Access Journals (Sweden)

    Tasić Nebojša M.

    2015-01-01

    Full Text Available Background/Aim. Some oligoelements are now investigated as possibly having a role in atherosclerosis. The aim of this study was to compare the concentrations of copper and zinc in the serum and carotid plaque and parameters of lipid metabolism in patients with different morphology of carotid atherosclerotic plaque. Methods. Carotid endarterectomy due to the significant atherosclerotic stenosis was performed in 91 patients (mean age 64 ± 7. The control group consisted of 27 patients (mean age 58 ± 9, without carotid atherosclerosis. Atheroscletoric plaques were divided into four morphological groups, according to ultrasonic and intraoperative characteristics. Copper and zinc concentrations in the plaque, carotid artery and serum were measured by atomic absorption spectrophotometry. Results. Serum copper concentrations were statistically significantly higher in the patients with hemorrhagic in comparison to those with calcified plaque (1.2 ± 0.9 μmol/L vs 0.7 ± 0.2 μmol/L, respectively; p = 0.021. Zinc concentrations were statistically significantly lower in plaques of the patients with fibrolipid in comparison to those with calcified plaques (22.1 ± 16.3 μg/g vs 38.4 ± 25.8 μg/g, respectively; p = 0.024. A negative significant correlation was found for zinc and triglycerides in the serum in all the patients (r = -0.52, p = 0.025. In the control group we also demonstrated a positive significant correlation for low-density lipoprotein cholesterol and copper in the serum (r = 0.54, p = 0.04. Conclusion. The data obtained in the current study are consistent with the hypothesis that high copper and lower zinc levels may contribute to atherosclerosis and its sequelae as factors in a multifactorial disease. Further studies are necessary in order to conclude whether high concentration of copper and zinc in the serum could be risk factors for atherosclesrosis.

  4. Molecular imaging of alpha v beta3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA.

    Science.gov (United States)

    Burtea, Carmen; Laurent, Sophie; Murariu, Oltea; Rattat, Dirk; Toubeau, Gérard; Verbruggen, Alfons; Vansthertem, David; Vander Elst, Luce; Muller, Robert N

    2008-04-01

    The integrin alpha v beta3 is highly expressed in atherosclerotic plaques by medial and intimal smooth muscle cells and by endothelial cells of angiogenic microvessels. In this study, we have assessed non-invasive molecular magnetic resonance imaging (MRI) of plaque-associated alpha v beta3 integrin expression on transgenic ApoE-/- mice with a low molecular weight peptidomimetic of Arg-Gly-Asp (mimRGD) grafted to gadolinium diethylenetriaminepentaacetate (Gd-DTPA-g-mimRGD). The analogous compound Eu-DTPA-g-mimRGD was employed for an in vivo competition experiment and to confirm the molecular targeting. The specific interaction of mimRGD conjugated to Gd-DTPA or to 99mTc-DTPA with alpha v beta3 integrin was furthermore confirmed on Jurkat T lymphocytes. The mimRGD was synthesized and conjugated to DTPA. DTPA-g-mimRGD was complexed with GdCl3.6H2O, EuCl3.6H2O, or with [99mTc(CO)3(H2O)3]+. MRI evaluation was performed on a 4.7 T Bruker imaging system. Blood pharmacokinetics of Gd-DTPA-g-mimRGD were assessed in Wistar rats and in c57bl/6j mice. The presence of angiogenic blood vessels and the expression of alpha v beta3 integrin were confirmed in aorta specimens by immunohistochemistry. Gd-DTPA-g-mimRGD produced a strong enhancement of the external structures of the aortic wall and of the more profound layers (possibly tunica media and intima). The aortic lumen seemed to be restrained and distorted. Pre-injection of Eu-DTPA-g-mimRGD diminished the Gd-DTPA-g-mimRGD binding to atherosclerotic plaque and confirmed the specific molecular targeting. A slower blood clearance was observed for Gd-DTPA-g-mimRGD, as indicated by a prolonged elimination half-life and a diminished total clearance. The new compound is potentially useful for the diagnosis of vulnerable atherosclerotic plaques and of other pathologies characterized by alpha v beta3 integrin expression, such as cancer and inflammation. The delayed blood clearance, the significant enhancement of the signal

  5. 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.)

  6. 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

  7. Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial Nitric Oxide Synthase

    Directory of Open Access Journals (Sweden)

    ML Rossi

    2009-06-01

    Full Text Available Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs and impaired bioavailabilty of nitric oxide (NO are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5’ nuclease assays (TaqMan™ PCRs to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA and 15 with acute coronary syndromes (ACS without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001 in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype.

  8. A finite element study of balloon expandable stent for plaque and arterial wall vulnerability assessment

    Science.gov (United States)

    Karimi, Alireza; Navidbakhsh, Mahdi; Razaghi, Reza

    2014-07-01

    The stresses induced within plaque tissues and arterial layers during stent expansion inside an atherosclerotic artery can be exceeded from the yield stresses of those tissues and, consequently, lead to plaque or arterial layer rupture. The distribution and magnitude of the stresses in each component involved in stenting might be clearly different for different plaque types and different arterial layers. In this study, a nonlinear finite element simulation was employed to investigate the effect of plaque composition (calcified, cellular, and hypocellular) on the stresses induced in the arterial layers (intima, media, and adventitia) during implantation of a balloon expandable coronary stent into a stenosed artery. The atherosclerotic artery was assumed to consist of a plaque and normal/healthy arterial tissues on its outer side. The results indicated a significant influence of plaque types on the maximum stresses induced within the plaque wall and arterial layers during stenting but not when computing maximum stress on the stent. The stress on the stiffest calcified plaque wall was in the fracture level (2.38 MPa), whereas cellular and hypocellular plaques remain stable owing to less stress on their walls. Regardless of plaque types, the highest von Mises stresses were observed on the stiffest intima layer, whereas the lowest stresses were seen to be located in less stiff media layer. The computed stresses on the intima layer were found to be high enough to initiate a rupture in this stiff layer. These findings suggest a higher risk of arterial vascular injury for the intima layer, while a lower risk of arterial injury for the media and adventitia layers.

  9. Selective removal of cholesteryl ester in atherosclerotic plaque by nanosecond pulsed laser at 5.75 μm for less-invasive laser angioplasty

    Science.gov (United States)

    Ishii, Katsunori; Tsukimoto, Hideki; Hazama, Hisanao; Awazu, Kunio

    2009-02-01

    Laser angioplasty, for example XeCl excimer laser coronary angioplasty (ELCA), has gained more attention for the treatment of serious stenosis blocked by plaque. Low degrees of thermal damage after ablation of atherosclerotic plaques have been achieved by ELCA. However, the large number of risks associated with the procedure, for example, dissections or perforations of the coronary arteries limits its application. A laser treatment technique with high ablation efficiency but low arterial wall injury is desirable. Mid-infrared laser with a wavelength of 5.75 µm is selectively well absorbed in C=O stretching vibration mode of ester bonds in cholesteryl ester. The purpose of this study is to determine the effectiveness of nanosecond pulsed laser at 5.75 µm irradiation for atherosclerotic plaques. We made a study on the irradiation effect to atherosclerotic plaques in tunica intima in a wet condition. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference-frequency generation, with a wavelength of 5.75 µm, a pulse width of 5 ns and a pulse duration of 10 Hz as a treatment light source, and a thoracic aorta of WHHLMI rabbit as an atherosclerosis model. As a result, less-invasive interaction parameters for removing atherosclerotic plaques were confirmed. This study shows that the nanosecond pulsed laser irradiation at 5.75 µm is a powerful tool for selective and less-invasive treatment of atherosclerotic plaques.

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

    Science.gov (United States)

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

    2017-01-01

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

  11. 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

    with elevated levels of fasting and postprandial plasma triglycerides (P=.0002 and P=.002), IDL cholesterol (P=.0009 and P=.006), and VLDL/chylomicron remnant cholesterol (P=.0003 and P=.0004) and triglycerides (P=.0003 and P=.003), the area under the plasma triglyceride curve 0 to 4 hours after a fatty meal (P......=.001): and body mass index (P=.0001). On ANCOVA, body mass index, fasting IDL cholesterol, and fasting plasma triglycerides were independent predictors of echo-lucency. Echo-lucency was associated with increased relative plaque lipid content (P=.02). Conclusions-Increased plasma levels of triglyceride......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...

  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. Elevated expression of mechanosensory polycystins in human carotid atherosclerotic plaques: association with p53 activation and disease severity.

    Science.gov (United States)

    Varela, Aimilia; Piperi, Christina; Sigala, Fragiska; Agrogiannis, George; Davos, Constantinos H; Andri, Maria-Anastasia; Manopoulos, Christos; Tsangaris, Sokrates; Basdra, Efthimia K; Papavassiliou, Athanasios G

    2015-08-19

    Atherosclerotic plaque formation is associated with irregular distribution of wall shear stress (WSS) that modulates endothelial function and integrity. Polycystins (PC)-1/-2 constitute a flow-sensing protein complex in endothelial cells, able to respond to WSS and induce cell-proliferation changes leading to atherosclerosis. An endothelial cell-culture system of measurable WSS was established to detect alterations in PCs expression under conditions of low- and high-oscillatory shear stress in vitro. PCs expression and p53 activation as a regulator of cell proliferation were further evaluated in vivo and in 69 advanced human carotid atherosclerotic plaques (AAPs). Increased PC-1/PC-2 expression was observed at 30-60 min of low shear stress (LSS) in endothelial cells. Elevated PC-1 expression at LSS was followed by p53 potentiation. PCs immunoreactivity localizes in areas with macrophage infiltration and neovascularization. PC-1 mRNA and protein levels were significantly higher than PC-2 in stable fibroatherotic (V) and unstable/complicated (VI) AAPs. Elevated PC-1 immunostaining was detected in AAPs from patients with diabetes mellitus, dyslipidemia, hypertension and carotid stenosis, at both arteries (50%) or in one artery (90%). PCs seem to participate in plaque formation and progression. Since PC-1 upregulation coincides with p38 and p53 activation, a potential interplay of these molecules in atherosclerosis induction is posed.

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

    Directory of Open Access Journals (Sweden)

    João L. A. A. Falcão

    2015-04-01

    Full Text Available Background: 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. Objectives: 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. Methods: 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%. Results: 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. Conclusions: 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.

  15. 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.

  16. 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.

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

    Science.gov (United States)

    Montecucco, Fabrizio; Steffens, Sabine; Mach, François

    2007-01-01

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

  18. 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.)

  19. Middle Cerebral Artery Atherosclerotic Plaques in Recent Small Subcortical Infarction: A Three-Dimensional High-resolution MR Study

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Zou

    2015-01-01

    Full Text Available Purpose. Conventional two-dimensional vessel wall imaging has been used to depict the middle cerebral artery (MCA wall in patients with recent small subcortical infarctions (RSSIs. However, its clinical use has been limited by restricted spatial coverage, low signal-to-noise ratio (SNR, and long scan time. We used a novel three-dimensional high-resolution MR imaging (3D HR-MRI technique to investigate the presence, locations, and contrast-enhanced patterns of MCA plaques and their relationship with RSSI. Methods. Nineteen consecutive patients with RSSI but no luminal stenosis on MR angiography were prospectively enrolled. 3D HR-MRI was performed using a T1w-SPACE sequence at 3.0 T. The presence, locations, and contrast-enhanced patterns of the MCA plaques on the ipsilateral and contralateral sides to the RSSI were analyzed. Results. Eighteen patients successfully completed the study. MCA atherosclerotic plaques occurred more frequently on the ipsilateral than the contralateral side to the RSSI (72.2% versus 33.3%, P=0.044. The occurrence of superiorly located plaques was significantly higher on the ipsilateral than the contralateral side of the MCA (66.7% versus 27.8%; P=0.044. Conclusions. Superiorly located plaques are closely associated with RSSI. 3D high-resolution vessel wall imaging may be a potential tool for etiologic assessment of ischemic stroke.

  20. The role of septal perforators and "myocardial bridging effect" in atherosclerotic plaque distribution in the coronary artery disease.

    Science.gov (United States)

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

    2015-01-01

    The distribution of atherosclerotic plaque burden in the human coronary arteries is not uniform. Plaques are located mostly in the left anterior descending artery (LAD), then in the right coronary artery (RCA), circumflex branch (LCx) and the left main coronary artery (LM) in a decreasing order of frequency. In the LAD and LCx, plaques tend to cluster within the proximal segment, while in the RCA their distribution is more uniform. Several factors have been involved in this phenomenon, particularly flow patterns in the left and right coronary artery. Nevertheless, it does not explain the difference in lesion frequency between the LAD and the LCx as these are both parts of the left coronary artery. Branching points are considered to be the risk points of atherosclerosis. In the LCx, the number of side branches is lower than in the LAD or RCA and there are no septal perforators with intramuscular courses like in the proximal third of the LAD and the posterior descending artery (PDA). We hypothesized that septal branches generate disturbed flow in the LAD and PDA in a similar fashion to the myocardial bridge (myocardial bridging effect). This coronary architecture determines the non-uniform plaque distribution in coronary arteries and LAD predisposition to plaque formation.

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

    Science.gov (United States)

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

    2015-01-01

    Summary The distribution of atherosclerotic plaque burden in the human coronary arteries is not uniform. Plaques are located mostly in the left anterior descending artery (LAD), then in the right coronary artery (RCA), circumflex branch (LCx) and the left main coronary artery (LM) in a decreasing order of frequency. In the LAD and LCx, plaques tend to cluster within the proximal segment, while in the RCA their distribution is more uniform. Several factors have been involved in this phenomenon, particularly flow patterns in the left and right coronary artery. Nevertheless, it does not explain the difference in lesion frequency between the LAD and the LCx as these are both parts of the left coronary artery. Branching points are considered to be the risk points of atherosclerosis. In the LCx, the number of side branches is lower than in the LAD or RCA and there are no septal perforators with intramuscular courses like in the proximal third of the LAD and the posterior descending artery (PDA). We hypothesized that septal branches generate disturbed flow in the LAD and PDA in a similar fashion to the myocardial bridge (myocardial bridging effect). This coronary architecture determines the non-uniform plaque distribution in coronary arteries and LAD predisposition to plaque formation. PMID:25922625

  2. 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.

  3. Evolution and rupture of vulnerable plaques: a review of mechanical effects

    Directory of Open Access Journals (Sweden)

    Assemat P

    2013-04-01

    Full Text Available Pauline Assemat, Kerry Hourigan Fluids Laboratory for Aeronautical and Industrial Research (FLAIR, Department of Mechanical and Aerospace Engineering and Division of Biological Engineering, Monash University, Melbourne, VIC, Australia Abstract: Atherosclerosis occurs as a result of the buildup and infiltration of lipid streaks in artery walls, leading to plaques. Understanding the development of atherosclerosis and plaque vulnerability is of critical importance, since plaque rupture can result in heart attack or stroke. Plaques can be divided into two distinct types: those that rupture (vulnerable and those that are less likely to rupture (stable. In the last few decades, researchers have been interested in studying the influence of the mechanical effects (blood shear stress, pressure forces, and structural stress on the plaque formation and rupture processes. In the literature, physiological experimental studies are limited by the complexity of in vivo experiments to study such effects, whereas the numerical approach often uses simplified models compared with realistic conditions, so that no general agreement of the mechanisms responsible for plaque formation has yet been reached. In addition, in a large number of cases, the presence of plaques in arteries is asymptomatic. The prediction of plaque rupture remains a complex question to elucidate, not only because of the interaction of numerous phenomena involved in this process (biological, chemical, and mechanical but also because of the large time scale on which plaques develop. The purpose of the present article is to review the current mechanical models used to describe the blood flow in arteries in the presence of plaques, as well as reviewing the literature treating the influence of mechanical effects on plaque formation, development, and rupture. Finally, some directions of research, including those being undertaken by the authors, are described. Keywords: atherosclerosis, rupture

  4. Three-dimensional imaging MS of lipids in atherosclerotic plaques: Open-source methods for reconstruction and analysis.

    Science.gov (United States)

    Patterson, Nathan H; Doonan, Robert J; Daskalopoulou, Stella S; Dufresne, Martin; Lenglet, Sébastien; Montecucco, Fabrizio; Thomas, Aurélien; Chaurand, Pierre

    2016-06-01

    Three-dimensional MALDI imaging MS (IMS) is a growing branch of IMS still requiring developments in methodology and technology to make the technique routinely accessible. Many challenges are simply a matter of producing 3D reconstructions and interpreting them in a timely fashion. In this aim and using analysis of lipids from atherosclerotic plaques from a human carotid and mouse aortic sinuses, we describe 3D reconstruction methods using open-source software that provides high-quality visualization and rapid interpretation through multivariate segmentation of the 3D IMS data. Multiple datasets were generated for each sample and we provide insight into simple means to correlate the separate datasets.

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

    Energy Technology Data Exchange (ETDEWEB)

    Henzler, Thomas, E-mail: Thomas.Henzler@umm.de [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Porubsky, Stefan [Department of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Kayed, Hany [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Harder, Nils [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Department of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Krissak, U. Radko; Meyer, Mathias [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Sueselbeck, Tim [1st Department of Medicine University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Marx, Alexander [Department of Pathology, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Michaely, Henrik [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany); Schoepf, U. Joseph [Department of Radiology and Radiological Science, Medical University of South Carolina, 169 Ashley Avenue, Charleston (United States)

    2011-10-15

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

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

    Directory of Open Access Journals (Sweden)

    Grimm Jochen M

    2012-11-01

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

  7. Effects of the direct lipoprotein-associated phospholipase A2 inhibitor darapladib on human coronary atherosclerotic plaque

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); H.M. Garcia-Garcia (Hector); P. Buszman (Pawel); P. Erne (Paul); S. Verheye (Stefan); M. Aschermann (Michael); H.J. Duckers (Henricus); O. Bleie (Oyvind); D. Dudek (Dariusz); H.E. Bøtker (Hans); C. von Birgelen (Clemens); D. D'Amico (Don); T. Hutchinson (Tammy); A. Zambanini (Andrew); F. Mastik (Frits); G.A. van Es (Gerrit Anne); A.F.W. van der Steen (Ton); D.G. Vince (Geoffrey); P. Ganz (Peter); C.W. Hamm (Christian); W. Wijns (William); A. Zalewski (Andrew)

    2008-01-01

    textabstractBackground - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation and cell death, rendering plaque vulnerable to rupture. Methods and Results - This study

  8. Effects of the direct lipoprotein-associated phospholipase A2 inhibitor darapladib on human coronary atherosclerotic plaque

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); H.M. Garcia-Garcia (Hector); P. Buszman (Pawel); P. Erne (Paul); S. Verheye (Stefan); M. Aschermann (Michael); H.J. Duckers (Henricus); O. Bleie (Oyvind); D. Dudek (Dariusz); H.E. Bøtker (Hans); C. von Birgelen (Clemens); D. D'Amico (Don); T. Hutchinson (Tammy); A. Zambanini (Andrew); F. Mastik (Frits); G.A. van Es (Gerrit Anne); A.F.W. van der Steen (Ton); D.G. Vince (Geoffrey); P. Ganz (Peter); C.W. Hamm (Christian); W. Wijns (William); A. Zalewski (Andrew)

    2008-01-01

    textabstractBackground - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation and cell death, rendering plaque vulnerable to rupture. Methods and Results - This study

  9. Detection of atherosclerotic plaque progression in the abdominal aorta of rabbits with 3T magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    MA Xiao-hai; ZHAO Lei; ZHAO Quan-ming; FENG Ting-ting; SHANG Jian-feng; ZHANG Zhao-qi

    2012-01-01

    Background With features of high tissue contrast,MRI can be used for the qualitative and quantitative evaluation of atherosclerosis plaques.In this study we investigated the development of atherosclerosis plaque with high resolution 3T MRI in a rabbit model and compared the findings with the histopathological results.Method Twenty male New Zealand white rabbits were randomly allocated into an experimental group (n=16) and a control group (n=4).Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding.Multiple sequences MRI examination (ToF,T1WI,T2WI,and CE T1WI) were performed at the 2nd,3rd,and 4th months after aortic denudation.Vessel wall thickness,total vessel area,lumen area,and vessel wall area were recorded.Plaque components were analyzed using histological results as a standard reference.Results Seventeen rabbits (14 in the experimental group and 3 in the control group) received all three MR examinations.Gradually,from 2 months to 4 months,vessel wall thickness and area in the experimental group increased significantly compared with the control group (P <0.01).In the lumen area progressive stenosis was not found,even a slight dilation had developed in the experimental group.Lipid,fibretic and calcified plaques can be differentiated by MR image.According to histological results,MRI had good performance in detection of lipid plaque.Conclusion MRI can be used to monitor progression of atherosclerosis and differentiate plaque components.

  10. [New insights towards catheter-based identification of vulnerable plaque

    NARCIS (Netherlands)

    G.A. Rodriguez-Granillo (Gaston); P.W.J.C. Serruys (Patrick); E.S. Regar (Eveline); J.A. Schaar (Johannes)

    2005-01-01

    textabstractSudden cardiac death or unheralded acute coronary syndromes are common initial manifestations of coronary atherosclerosis and most such events occur at sites of non-flow limiting coronary atherosclerosis. Autopsy data suggests that plaque composition is a key determinant of the propensit

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hetterich, Holger; Fill, Sandra [Klinikum der Ludwig-Maximilians-Univ., Muenchen (Germany). Inst. fuer Klinische Radiologie; Herzen, Julia [Technische Univ. Muenchen, Garching (Germany). Physik-Dept. und Inst. fuer Medizintechnik; Helmholtz-Zentrum Geesthacht, Geesthacht (Germany). Zentrum fuer Materialforschung] [and others

    2013-10-01

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

  13. Prevalence of eight putative periodontal pathogens in atherosclerotic plaque of coronary artery disease patients and comparing them with noncardiac subjects: A case-control study

    Directory of Open Access Journals (Sweden)

    Jaideep Mahendra

    2015-01-01

    Conclusion: It is concluded that CAD subjects had higher prevalence of periodontal pathogens in subgingival biofilms as compared to the non cardiac subjects. Further, the number of bacteria was significantly associated between the subgingival and atherosclerotic plaques of the cardiac patients in south Indian population.

  14. 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

  15. 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

  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

    .4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P aged 61 or 71 years, with moderate or very high SCORE or intermediate or high FRS (all P aged 41, 51 or 61 years......, with moderate SCORE or with high-intermediate or high FRS (all P aged 51 years (P aged 51 [hazard ratio 2.7 (1.6-4.8)] and 61...... and especially atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 0.73/1.06 mg/mmol (men/women) added prognostic information in individuals aged 51 or 61 years or with moderate or intermediate risk....

  17. 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)

    Boekhorst, B. C. M. Te; 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 inversi

  18. 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.

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

    Science.gov (United States)

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

    2007-02-01

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

  20. 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.

  1. In Vivo/Ex Vivo MRI-Based 3D Non-Newtonian FSI Models for Human Atherosclerotic Plaques Compared with Fluid/Wall-Only Models.

    Science.gov (United States)

    Yang, Chun; Tang, Dalin; Yuan, Chun; Hatsukami, Thomas S; Zheng, Jie; Woodard, Pamela K

    2007-01-01

    It has been recognized that fluid-structure interactions (FSI) play an important role in cardiovascular disease initiation and development. However, in vivo MRI multi-component FSI models for human carotid atherosclerotic plaques with bifurcation and quantitative comparisons of FSI models with fluid-only or structure-only models are currently lacking in the literature. A 3D non-Newtonian multi-component FSI model based on in vivo/ex vivo MRI images for human atherosclerotic plaques was introduced to investigate flow and plaque stress/strain behaviors which may be related to plaque progression and rupture. Both artery wall and plaque components were assumed to be hyperelastic, isotropic, incompressible and homogeneous. Blood flow was assumed to be laminar, non-Newtonian, viscous and incompressible. In vivo/ex vivo MRI images were acquired using histologically-validated multi-spectral MRI protocols. The 3D FSI models were solved and results were compared with those from a Newtonian FSI model and wall-only/fluid-only models. A 145% difference in maximum principal stresses (Stress-P(1)) between the FSI and wall-only models and 40% difference in flow maximum shear stress (MSS) between the FSI and fluid-only models were found at the throat of the plaque using a severe plaque sample (70% severity by diameter). Flow maximum shear stress (MSS) from the rigid wall model is much higher (20-40% in maximum MSS values, 100-150% in stagnation region) than those from FSI models.

  2. 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

    before carotid endarterectomy. Plaque mRNA expression of the inflammatory cytokine interleukin 18 (IL-18), the macrophage-specific marker CD68 and the two proteinases, Cathepsin K and matrix metalloproteinase 9 (MMP-9), were quantified using real-time quantitative polymerase chain reaction. RESULTS......: Consistent up-regulation of CD68 (3.8-fold+/-0.9; mean+/-standard error), Cathepsin K (2.1-fold+/-0.5), MMP-9 (122-fold+/-65) and IL-18 (3.4-fold+/-0.7) were found in the plaques, compared to reference-artery specimens. The FDG uptake by plaques was strongly correlated with CD68 gene expression (r=0.71, P=0.......02). Any correlations with Cathepsin K, MMP-9 or IL-18 gene expression were weaker. CONCLUSIONS: FDG-PET uptake in carotid plaques is correlated to gene expression of CD68 and other molecular markers of inflammation and vulnerability Udgivelsesdato: 2009/6...

  3. 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...

  4. Feasibility of Vascular Endothelial Growth Factor Imaging in Human Atherosclerotic Plaque Using 89Zr-Bevacizumab Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Reza Golestani

    2013-06-01

    Full Text Available Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-bevacizumab micro-positron emission tomography (PET was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%Inc/g and tissue to background ratio were determined. A 10-fold higher accumulation of 89Zr-bevacizumab compared to 111In-IgG uptake was demonstrated by gamma counting. The mean %Inc/ghot spot was 2.2 ± 0.9 with a hot spot to background ratio of 3.6 ± 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (ρ = .74, p < .001. It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.

  5. Selective ablation of WHHLMI rabbit atherosclerotic plaque by quantum cascade laser in the 5.7 μm wavelength range for less-invasive laser angioplasty

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Akikusa, Naota; Edamura, Tadataka; Yoshida, Harumasa; Awazu, Kunio

    2013-06-01

    We investigated the potential of a compact and high-power quantum cascade laser (QCL) in the 5.7 μm wavelength range for less-invasive laser angioplasty. Atherosclerotic plaques consist mainly of cholesteryl esters. Radiation at a wavelength of 5.75 μm is strongly absorbed in C=O stretching vibration mode of cholesteryl esters. Our previous study achieved to make cutting differences between a normal artery and an atherosclerotic lesions using nanosecond pulsed laser by difference-frequency generation (DFG laser) at the wavelength of 5.75 μm. For applying this technique to clinical treatment, a compact laser device is required. In this study, QCL irradiation effects to a porcine normal aorta were compared with DFG laser. Subsequently, QCL irradiation effects on an atherosclerotic aorta of myocardial infarction-prone Watanabe heritable hyperlipidemic rabbit (WHHLMI rabbit) and a normal rabbit aorta were observed. As a result, the QCL could make cutting differences between the rabbit atherosclerotic and normal aortas. On the other hand, the QCL induced more thermal damage to porcine normal aorta than the DFG laser at the irradiation condition of comparable ablation depths. In conclusion, the possibility of less-invasive and selective treatment of atherosclerotic plaques using the QCL in the 5.7 μm wavelength range was revealed, although improvement of QCL was required to prevent the thermal damage of a normal artery.

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

    Science.gov (United States)

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

    2017-01-01

    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. PMID:28699976

  7. Selective treatment of atherosclerotic plaques using nanosecond pulsed laser with a wavelength of 5.75 μm for less-invasive laser angioplasty

    Science.gov (United States)

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

    2009-07-01

    XeCl excimer laser coronary angioplasty (ELCA), has gained more attention for the treatment of serious stenosis blocked by plaque. Low degrees of thermal damage after ablation of atherosclerotic plaques have been achieved by ELCA. However, the large number of risks associated with the procedure, for example, dissections or perforations of the coronary arteries limits its application. The laser treatment technique with high ablation efficiency but low arterial wall injury is desirable. Mid-infrared laser with a wavelength of 5.75 μm is selectively well absorbed in C=O stretching vibration mode of ester bonds in cholesteryl ester. We studied the effectiveness of nanosecond pulsed laser at 5.75 μm for novel less-invasive laser angioplasty. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference-frequency generation, at 5.75 μm, a pulse width of 5 ns and a pulse repetition rate of 10 Hz as a treatment light source, and a thoracic aorta of WHHLMI rabbit as an atherosclerosis model. As a result, less-invasive treatment parameters for removing atherosclerotic plaques in a wet condition were confirmed. This study shows that the nanosecond pulsed laser irradiation at 5.75 μm is a powerful tool for selective and less-invasive treatment of atherosclerotic plaques.

  8. Effects of the PPARγ agonist pioglitazone on coronary atherosclerotic plaque composition and plaque progression in non-diabetic patients: a double-center, randomized controlled VH-IVUS pilot-trial.

    Science.gov (United States)

    Christoph, Marian; Herold, Joerg; Berg-Holldack, Anna; Rauwolf, Thomas; Ziemssen, Tjalf; Schmeisser, Alexander; Weinert, Sönke; Ebner, Bernd; Said, Samir; Strasser, Ruth H; Braun-Dullaeus, Ruediger C

    2015-05-01

    Despite the advanced therapy with statins, antithrombotics and antihypertensive agents, the medical treatment of coronary artery disease is less than optimal. Therefore, additional therapeutic anti-atherosclerotic options are desirable. This VH-IVUS study (intravascular ultrasonography with virtual histology) was performed to assess the potential anti-atherogenic effect of the PPARγ agonist pioglitazone in non-diabetic patients. A total of 86 non-culprit atherosclerotic lesions in 54 patients with acute coronary syndrome were observed in a 9-month prospective, double-blind, and placebo-controlled IVUS study. Patients were randomized to receive either 30 mg pioglitazone (Pio) or placebo (Plac). As primary efficacy parameter, the change of relative plaque content of necrotic core was determined by serial VH-IVUS analyses. Main secondary endpoint was the change of total plaque volume. In contrast to placebo, in the pioglitazone-treated group, the relative plaque content of necrotic core decreased significantly (Pio -1.3 ± 6.9% vs. Plac +2.6 ± 6.5%, p < 0.01). In comparison to the placebo group, the plaques in pioglitazone-treated patients showed significantly greater reduction of the total plaque volume (Pio -16.1 ± 26.4 mm3 vs. Plac -1.8 ± 30.9 mm3, p = 0.02). Treatment with a PPARγ agonist in non-diabetic patients results in a coronary artery plaque stabilization on top of usual medical care.

  9. 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.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Hanna E Auvinen

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

  12. The lipid-rich core region of human atherosclerotic fibrous plaques. Prevalence of small lipid droplets and vesicles by electron microscopy.

    OpenAIRE

    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 aq...

  13. The lipid-rich core region of human atherosclerotic fibrous plaques. Prevalence of small lipid droplets and vesicles by electron microscopy.

    OpenAIRE

    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 aq...

  14. Tracking Monocyte Recruitment and Macrophage Accumulation in Atherosclerotic Plaque Progression Using a Novel hCD68GFP/ApoE−/− Reporter Mouse—Brief Report

    Science.gov (United States)

    Iqbal, Asif J.; Jones, Daniel; Patel, Jyoti; Coutinho, Patricia; Taylor, Lewis; Greaves, David R.; Channon, Keith M.

    2017-01-01

    Objective— To create a model of atherosclerosis using green fluorescent protein (GFP)–targeted monocytes/macrophages, allowing analysis of both endogenous GFP+ and adoptively transferred GFP+ myeloid cells in arterial inflammation. Approach and Results— hCD68GFP reporter mice were crossed with ApoE−/− mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II–induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP+ expression in CD11b+/CD64+, CD11c+/MHC-IIHI, and CD11b+/F4/80+ myeloid cells. Adoptive transfer of GFP+ monocytes demonstrated monocyte recruitment to both adventitia and atherosclerotic plaque, throughout the aortic root, within 72 hours. We demonstrated the biological utility of hCD68GFP monocytes by comparing the recruitment of wild-type and CCR2−/− monocytes to sites of inflammation. Conclusions— hCD68GFP/ApoE−/− mice provide a new approach to study macrophage accumulation in atherosclerotic plaque progression and to identify cells recruited from adoptively transferred monocytes. PMID:27908893

  15. Mycophenolate mofetil (MMF): firing at the atherosclerotic plaque from different angles?

    Science.gov (United States)

    van Leuven, Sander I; Kastelein, John J P; Allison, Anthony C; Hayden, Michael R; Stroes, Erik S G

    2006-02-01

    Atherosclerosis is characterized by a persistent, low-grade inflammatory state in which immune cell activation is inseparably linked to plaque formation and destabilization. The T-lymphocyte in particular has emerged as a pivotal player throughout the course of atherogenesis. As a consequence, the concept that immune modulation is a suitable target for cardiovascular prevention is currently an important focus of research. Mycophenolate mofetil (MMF) has emerged as a non-competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) that exerts cytostatic effects, particularly on proliferating T-lymphocytes. In addition, MMF has other immune-modulating effects, such as downregulation of the expression of adhesion molecules and attenuation of monocyte and macrophage responses. Given the added benefit that MMF is well tolerated, this immunosuppressive agent constitutes an attractive candidate for the modulation of inflammatory activation in atherogenesis. The present review provides an overview of the potential anti-atherogenic properties of MMF.

  16. 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

    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......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...... by activated monocytes (and possibly macrophages) and is a highly basic protein, it would be expected to associate with polyanions such as the glycosaminoglycans of the extracellular matrix, and might result in damage being localized at such sites. In this study proteins extracted from extracellular matrix...

  17. Effects of Low Carbohydrate High Protein (LCHP) diet on atherosclerotic plaque phenotype in ApoE/LDLR-/- mice: FT-IR and Raman imaging.

    Science.gov (United States)

    Wrobel, T P; Marzec, K M; Chlopicki, S; Maślak, E; Jasztal, A; Franczyk-Żarów, M; Czyżyńska-Cichoń, I; Moszkowski, T; Kostogrys, R B; Baranska, M

    2015-09-22

    Low Carbohydrate High Protein (LCHP) diet displays pro-atherogenic effects, however, the exact mechanisms involved are still unclear. Here, with the use of vibrational imaging, such as Fourier transform infrared (FT-IR) and Raman (RS) spectroscopies, we characterize biochemical content of plaques in Brachiocephalic Arteries (BCA) from ApoE/LDLR(-/-) mice fed LCHP diet as compared to control, recomended by American Institute of Nutrition, AIN diet. FT-IR images were taken from 6-10 sections of BCA from each mice and were complemented with RS measurements with higher spatial resolution of chosen areas of plaque sections. In aortic plaques from LCHP fed ApoE/LDLR(-/-) mice, the content of cholesterol and cholesterol esters was increased, while that of proteins was decreased as evidenced by global FT-IR analysis. High resolution imaging by RS identified necrotic core/foam cells, lipids (including cholesterol crystals), calcium mineralization and fibrous cap. The decreased relative thickness of the outer fibrous cap and the presence of buried caps were prominent features of the plaques in ApoE/LDLR(-/-) mice fed LCHP diet. In conclusion, FT-IR and Raman-based imaging provided a complementary insight into the biochemical composition of the plaque suggesting that LCHP diet increased plaque cholesterol and cholesterol esters contents of atherosclerotic plaque, supporting the cholesterol-driven pathogenesis of LCHP-induced atherogenesis.

  18. Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, and mortality: A systematic review and meta-analyses.

    Science.gov (United States)

    Gorgui, Jessica; Gasbarrino, Karina; Georgakis, Marios K; Karalexi, Maria A; Nauche, Bénédicte; Petridou, Eleni Th; Daskalopoulou, Stella S

    2017-04-01

    Low circulating levels of adiponectin, an anti-inflammatory and vasculoprotective adipokine, are associated with obesity, type 2 diabetes, and atherosclerotic disease. Presence of unstable plaques in the carotid artery is a known etiological factor causing ischemic strokes. Herein, we systematically reviewed the association between circulating adiponectin and progression of carotid atherosclerotic disease, particularly evaluating the occurrence of (1) carotid atherosclerotic plaques, (2) ischemic stroke, and (3) mortality in subjects who suffered a previous ischemic stroke. Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The effect size and 95% confidence intervals (CIs) of the individual studies were pooled using fixed-effect or random-effect models. The quality of the eligible studies was evaluated using the Newcastle-Ottawa quality assessment scale. Sensitivity, subgroup, and meta-regression analyses were performed to address the impact of various risk factors on the association between adiponectin and ischemic stroke risk. Twelve studies fulfilled the inclusion criteria for 3 independent meta-analyses. The association of increasing circulating adiponectin levels (5μg/mL-increment) with presence of carotid plaque was not conclusive (n=327; OR: 1.07; 95% CI: 0.85-1.35; 2 studies), whereas high adiponectin levels showed a significant 8% increase in risk of ischemic stroke (n=13,683; 7 studies), with a more sizable association observed among men compared to women. HDL was observed to have a marginal effect on the association between adiponectin and ischemic stroke, while other evaluated parameters were not found to be effect modifiers. A non-significant association of adiponectin with mortality was yielded (n=663; OR: 2.58; 95% CI: 0.69-9.62; 3 studies). Although no publication bias was evident, there was significant between-study heterogeneity in most analyses. It appears that the direction

  19. Mass Transport and Shear Stress as Mediators of Flow Effects on Atherosclerotic Plaque Origin and Growth

    Science.gov (United States)

    Gorder, Riley; Aliseda, Alberto

    2009-11-01

    The carotid artery bifurcation (CAB) is one of the leading site for atherosclerosis, a major cause of mortality and morbidity in the developed world. The specific mechanisms by which perturbed flow at the bifurcation and in the carotid bulge promotes plaque formation and growth are not fully understood. Shear stress, mass transport, and flow residence times are considered dominant factors. Shear stress causes restructuring of endothelial cells at the arterial wall which changes the wall's permeability. Long residence times are associated with enhanced mass transport through increased diffusion of lipids and white blood cells into the arterial wall. Although momentum and mass transfer are traditionally coupled by correlations similar to Reynolds Analogy, the complex flow patterns present in this region due to the pulsatile, transitional, detached flow associated with the complex geometry makes the validity of commonly accepted assumptions uncertain. We create solid models of the CAB from MRI or ultrasound medical images, build flow phantoms on clear polyester resin and use an IOR matching, blood mimicking, working fluid. Using PIV and dye injection techniques the shear stress and scalar transport are experimentally investigated. Our goal is to establish a quantitative relationship between momentum and mass transfer under a wide range of physiologically normal and pathological conditions.

  20. Vulnerable Plaque

    Science.gov (United States)

    ... Kawasaki Disease Long Q-T Syndrome Marfan Syndrome Metabolic Syndrome Mitral Valve Prolapse Myocardial Bridge Myocarditis Obstructive Sleep Apnea Pericarditis Peripheral Vascular Disease Rheumatic Fever Sick Sinus Syndrome Silent Ischemia Stroke Sudden ...

  1. {sup 18}F-FDG PET and intravascular ultrasonography (IVUS) images compared with histology of atherosclerotic plaques: {sup 18}F-FDG accumulates in foamy macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Ishino, Seigo [Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, Fujisawa (Japan); Takeda Pharmaceutical Company Limited, Biomolecular Research Laboratories, Pharmaceutical Research Division, Fujisawa, Kanagawa (Japan); Ogawa, Mikako; Magata, Yasuhiro [Hamamatsu University School of Medicine, Medical Photonics Research Center, Hamamatsu (Japan); Mori, Ikuo; Nishimura, Satoshi; Ikeda, Shota; Sugita, Taku; Oikawa, Tatsuo; Horiguchi, Takashi [Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, Fujisawa (Japan)

    2014-04-15

    Intravascular ultrasonography (IVUS) and {sup 18}F-FDG PET have been used to evaluate the efficacy of antiatherosclerosis drugs. These two modalities image different characteristics of atherosclerotic plaques, and a comparison of IVUS and PET images with histology has not been performed. The aim of this study was to align IVUS and PET images using anatomic landmarks in Watanabe heritable hyperlipidaemic (WHHL) rabbits, enabling comparison of their depiction of aortic atherosclerosis. Cellular {sup 18}F-FDG localization was evaluated by {sup 3}H-FDG microautoradiography (micro-ARG). A total of 19 WHHL rabbits (7 months of age) were divided into three groups: baseline (n = 6), 3 months (n = 4), and 6 months (n = 9). PET, IVUS and histological images of the same aortic segments were analysed. Infiltration by foamy macrophages was scored from 0 to IV using haematoxylin and eosin (H and E) and antimacrophage immunohistochemical staining, and compared with {sup 3}H-FDG micro-ARG findings in two additional WHHL rabbits. IVUS images did not identify foamy macrophage deposition but revealed the area of intimal lesions (r = 0.87). {sup 18}F-FDG PET revealed foamy macrophage distribution in the plaques. The intensity of {sup 18}F-FDG uptake was correlated positively with the degree of foamy macrophage infiltration. Micro-ARG showed identical {sup 3}H-FDG accumulation in the foamy macrophages surrounding the lipid core of the plaques. F-FDG PET localized and quantified the degree of infiltration of foamy macrophages in atherosclerotic lesions. IVUS defined the size of lesions. {sup 18}F-FDG PET is a promising imaging technique for evaluating atherosclerosis and for monitoring changes in the composition of atherosclerotic plaques affecting their stability. (orig.)

  2. 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 colesterol remanescente poderiam ter maior risco cardiovascular residual. determinar a prevalência de discordância lipídica em uma população de prevenção primária e analisar as variáveis clínicas com ela associadas; investigar a associação de discordância lipídica e colesterol remanescente calculado com a presença de placa carotídea. Pacientes de prevenção primária sem diabetes ou sem terapia hipolipemiante foram incluídos. Independentemente do nível de LDL-C, definiu-se "discordância lipídica" como um valor de não HDL-C excedendo em 30 mg/dl aquele de LDL-C. Calculou-se o colesterol remanescente como colesterol total menos HDL-C menos LDL-C na presença de triglicerídeos colesterol remanescente calculado e placa carotídea. Discordância lipídica e presença de nível mais alto de colesterol remanescente calculado acham-se associados com aterosclerose subclínica. Nossos achados podem ser usados para aprimorar a avaliação de risco cardiovascular residual.

  3. Chocolate consumption is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study.

    Science.gov (United States)

    Djoussé, Luc; Hopkins, Paul N; Arnett, Donna K; Pankow, James S; Borecki, Ingrid; North, Kari E; Curtis Ellison, R

    2011-02-01

    While a diet rich in anti-oxidant has been favorably associated with coronary disease and hypertension, limited data have evaluated the influence of such diet on subclinical disease. Thus, we sought to examine whether chocolate consumption is associated with calcified atherosclerotic plaque in the coronary arteries (CAC). In a cross-sectional design, we studied 2217 participants of the NHLBI Family Heart Study. Chocolate consumption was assessed by a semi-quantitative food frequency questionnaire and 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. There was an inverse association between frequency of chocolate consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.94 (0.66-1.35), 0.78 (0.53-1.13), and 0.68 (0.48-0.97) for chocolate consumption of 0, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.022), adjusting for age, sex, energy intake, waist-hip ratio, education, smoking, alcohol consumption, ratio of total-to-HDL-cholesterol, non-chocolate candy, and diabetes mellitus. Controlling for additional confounders did not alter the findings. Exclusion of subjects with coronary heart disease or diabetes mellitus did not materially change the odds ratio estimates but did modestly decrease the overall significance (p = 0.07). These data suggest that chocolate consumption might be inversely associated with prevalent CAC. Published by Elsevier Ltd.

  4. Correlation of three grades with carotid atherosclerotic plaque by the ultrasound in middle-aged patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    Jian-Ping Ru; Qing-Hua Yang; Xian-Da Jia

    2017-01-01

    Objective:To explore the correlation of different hypertension grades with carotid atherosclerotic plaque in middle-aged patients with hypertension.Methods:A total of 300 patients with primary hypertension who were admitted in the Cardiology Department and Neurology Department of our hospital from January, 2015 to September, 2016 were included in the study and divided into 3 groups with 100 cases in each group according to the hypertension grade criteria. Moreover, 100 normal individuals who came for physical examinations were served as the control group. TCD was used to detect MCA, ACA, PCA, VA1, and BA. CDFI was used to detect CCA, ICA, ECA, and VA2. EDV, PSV, PI, and RI were detected, respectively. The nitrate reductase colorimetric method was used to detect NO, MDA, and SOD.Results:PSV and EDV in the internal carotid artery system in patients with hypertension were significantly reduced (P<0.05), while PI and RI were significantly increased (P<0.05); moreover, with the increasing of hypertension grading, PSV and EDV were gradually reduced, while PI and RI were increased. PSV and EDV in the vertebral artery system in patients with hypertension were significantly reduced (P<0.05), while PI and RI were significantly increased (P<0.05); moreover, with the increasing of hypertension grading, PSV and EDV were gradually reduced, while PI and RI were increased. SOD and NO in patients with hypertension were significantly lower than those in the control group (P<0.05), while MDA was significantly higher than that in the control group (P<0.05); moreover, with the increasing of hypertension grading, SOD and NO were gradually reduced, while MDA was gradually increased.Conclusions: TCD in combined with CDFI can make a comprehensive evaluation of hemodynamic indicators of intracranial and extracranial vessels in patients with hypertension, and is of great significance in the early detection of intracranial and extracranial arteriosclerosis.

  5. Positron emission tomography of the vulnerable atherosclerotic plaque in man – a contemporary review

    DEFF Research Database (Denmark)

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

    2014-01-01

    Atherosclerosis is the primary underlying cause of cardiovascular disease (CVD). It is the leading cause of morbidity and mortality in the Western world today and is set to become the prevailing disease and major cause of death worldwide by 2020. In the 1950s surgical intervention was introduced ...

  6. Pregnancy-associated plasma protein-A and the vulnerable plaque

    DEFF Research Database (Denmark)

    Jespersen, Camilla H B; Vestergaard, Kirstine R; Schou, Morten

    2014-01-01

    For more than a decade, pregnancy-associated plasma protein-A (PAPP-A) has been examined for its relation to acute coronary syndrome (ACS) and the vulnerable plaque. This review summarizes the current knowledge of plasma PAPP-A in relation to nonpregnant individuals focusing on patients with ACS,......, discusses its use as a possible biomarker for diagnosis and prognosis in ACS, briefly describes the challenges in different assay technologies and describes the effect of heparin administration on PAPP-A concentrations in plasma....

  7. The interaction of serum and arterial lipoproteins with elastin of the arterial intima and its role in the lipid accumulation in atherosclerotic plaques.

    Science.gov (United States)

    Kramsch, D M; Hollander, W

    1973-02-01

    Arterial elastin appears to be a proteinlipid complex with the lipid component being bound to elastin peptide groups. In atherosclerotic lesions the lipid content of elastin increases progressively with increasing severity of atherosclerosis. The increases in the lipid content of plaque elastin are mainly due to large increases in cholesterol with about 80% of the cholesterol being cholesterol ester. This deposition of cholesterol in elastin accounts for a substantial part of the total cholesterol accumulation in atherosclerotic lesions of all stages. The present in vitro study suggests that the mechanism involved in the deposition of lipids in arterial elastin may be an interaction of the elastin protein with serum or arterial low density or very low density lipoproteins (LDL and VLDL) resulting in a transfer of lipids, but not of lipoprotein protein to the elastin. No significant lipid transfer occurred from the high density lipoproteins or chylomicrons. The amount of lipid taken up by plaque elastin was strikingly higher than by normal elastin and consisted mainly of cholesterol with over 80% of the cholesterol being cholesterol ester. The precondition for the lipid accumulation in plaque elastin appeared to be an altered amino acid composition of the elastin protein consisting of an increase in polar amino acids and a reduction in cross-linking amino acids. Subsequent treatment of lipoprotein-incubated arterial elastin with hot alkali and apolipoproteins did not reverse the binding of lipoprotein lipid to diseased elastin.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-15

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

  9. Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3

    Science.gov (United States)

    Solanki, Sumeet; Dube, Prabhatchandra R.; Birnbaumer, Lutz; Vazquez, Guillermo

    2017-01-01

    In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr−/−) mice with macrophage-specific loss of Trpc3 (MacTrpc3−/−/Ldlr−/− → Ldlr−/−). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3−/−/Ldlr−/− → Ldlr−/− mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis. PMID:28186192

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice. METHODS AND RESULTS: To determine the origin of SMCs after spontaneous plaque disruption......, irradiated 18-month-old apoE-/- mice were reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE-/- mice and examined when they died up to 9 months later. Plaque hemorrhage, indicating previous plaque disruption, was widely present, but no bone marrow-derived e......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...

  11. RNAseq based transcriptomics study of SMCs from carotid atherosclerotic plaque: BMP2 and IDs proteins are crucial regulators of plaque stability.

    Science.gov (United States)

    Alloza, Iraide; Goikuria, Haize; Idro, Juan Luis; Triviño, Juan Carlos; Fernández Velasco, José María; Elizagaray, Elena; García-Barcina, María; Montoya-Murillo, Genoveva; Sarasola, Esther; Vega Manrique, Reyes; Freijo, Maria Del Mar; Vandenbroeck, Koen

    2017-06-14

    Carotid artery atherosclerosis is a risk factor to develop cerebrovascular disease. Atheroma plaque can become instable and provoke a cerebrovascular event or else remain stable as asymptomatic type. The exact mechanism involved in plaque destabilization is not known but includes among other events smooth muscle cell (SMC) differentiation. The goal of this study was to perform thorough analysis of gene expression differences in SMCs isolated from carotid symptomatic versus asymptomatic plaques. Comparative transcriptomics analysis of SMCs based on RNAseq technology identified 67 significant differentially expressed genes and 143 significant differentially expressed isoforms in symptomatic SMCs compared with asymptomatic. 37 of top-scoring genes were further validated by digital PCR. Enrichment and network analysis shows that the gene expression pattern of SMCs from stable asymptomatic plaques is suggestive for an osteogenic phenotype, while that of SMCs from unstable symptomatic plaque correlates with a senescence-like phenotype. Osteogenic-like phenotype SMCs may positively affect carotid atheroma plaque through participation in plaque stabilization via bone formation processes. On the other hand, plaques containing senescence-like phenotype SMCs may be more prone to rupture. Our results substantiate an important role of SMCs in carotid atheroma plaque disruption.

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

    Directory of Open Access Journals (Sweden)

    Mei Li

    2015-01-01

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

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

    NARCIS (Netherlands)

    T.T. Keller (Tymen); J.J. van der Meer (Jelger); P. Teeling (Peter); K.F. van der Sluijs (Koenraad); M.M. Idu (Mirza); G.F. Rimmelzwaan (Guus); M. Levi (Michael); A.C. van der Wal (Allard); O.J. de Boer (Onno)

    2008-01-01

    textabstractBACKGROUND AND PURPOSE - Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the

  14. Magnetic resonance imaging of carotid atherosclerotic plaque%颈动脉粥样硬化斑块的磁共振成像

    Institute of Scientific and Technical Information of China (English)

    杨松; 周志明; 徐格林; 刘新峰

    2009-01-01

    Stroke is one of the diseases that seriously threats the health of the elderly, and atherosclerosis is the main cause of ischemic stroke. Became it is closely associated with stroke, carotid carotid atherosclerosis has been one of the research hot spots in neurology. In recent years, the development of MRI techniques has provided a new approach for the qualitative and quantitative analysis of atherosclerotic plaque, and has reflected its unique superiority, This article reviews the applications of MRI in the evaluation of carotid atherosclerotic plaques.%卒中足严苇威胁老年人健康的疾病之一,动脉粥样硬化是导致缺血性卒中的主要原因.由于与卒中存在密切联系.颈动脉粥样硬化一直是神经科的研究热点之一.近年来,MRI技术的发展为动脉粥样硬化斑块的定性和定量分析提供了一条新的途径,并体现出其独特的优越性.文章对MRI在颈动脉斑块评价中的应用做了综述.

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

    Directory of Open Access Journals (Sweden)

    Saskia J. H. Brinkmann

    2015-05-01

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

  16. [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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  18. Single-Chain VEGF/Cy5.5 Targeting VEGF Receptors to Indicate Atherosclerotic Plaque Instability

    NARCIS (Netherlands)

    Lam, Ming Kai; Al-Ansari, Sali; van Dam, Gooitzen M.; Tio, Rene A.; Breek, Jan-Cees; Slart, Riemer H. J. A.; Hillebrands, Jan-Luuk; Zeebregts, Clark J.

    2013-01-01

    Unstable plaques may cause clinical events. Plaque destabilization results from the synergy between intraplaque angiogenesis and inflammation. Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are considered to be involved in these processes. We investigated the efficacy of the a

  19. The pathological changes of inflammatory cells,smooth muscle cell and neo-vessels in the vulnerable carotid atherosclerosis plaque

    Institute of Scientific and Technical Information of China (English)

    吕鹤

    2006-01-01

    Objective To study the inflammation, smooth muscle cells and neovessels change in the vulnerable carotid atherosclerosis plaque. Methods 6 male patients, aged between 66~73 years old, had the history of stroke or transient cerebral ischemic attacks of internal carotid artery system in a few days to 5 months. MRI and DSA re-

  20. Atherosclerotic plaque components characterization and macrophage infiltration identification by intravascular ultrasound elastography based on b-mode analysis: validation in vivo.

    Science.gov (United States)

    Zhang, Peng-Fei; Su, Hai-Jun; Zhang, Mei; Li, Ji-Fu; Liu, Chun-Xi; Ding, Shi-Fang; Miao, Ya; Chen, Liang; Li, Xiao-Nan; Yi, Xin; Zhang, Yun

    2011-01-01

    Intravascular ultrasound elastography (IVUSE) is a promising imaging technique for early investigation of vulnerable plaques. Compared to radiofrequency signal processing, digital B-mode analysis is simple and of higher portability. However, rare studies have been reported validating the latter technique in vivo. In this study, we developed an IVUSE computer software system involving semi-automatic border delineation and block-matching algorithm and validated the system in vivo. Seven minipigs were fed with atherogenic diet for 40 weeks. For each pig, the endothelium of one side of the renal arteries was denuded at the fifth week. With cross-correlation analysis, Lagrangian strain was calculated from two intravascular ultrasound images acquired in situ. Sixty regions of interests were selected from 35 elastograms matched well with the corresponding histological slices. Plaque types within these regions were classified as fibrous, fibro-fatty or fatty on Masson's trichrome and Oil-red O staining. Macrophage infiltration was also evaluated with immunohistology. Comparison between the mean strain value of the region of interest and the histological results revealed significant differences in strain values among different plaque types and non-diseased artery walls. The extent of macrophage infiltration was found to be correlated positively with strain values. For identification of fibro-fatty and fibrous plaques and macrophage infiltration, the system showed high sensitivity (93, 96 and 92%, respectively) and specificity (89, 76 and 66%, respectively), as revealed by receiver operating characteristic analysis. Our IVUSE system based on B-mode analysis is capable of characterizing fibrous and fibro-fatty plaques and macrophage intensity, thus holds potential for identifying vulnerable plaque.

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

    Directory of Open Access Journals (Sweden)

    Ilonka Rohm

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-15

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

  3. Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice

    OpenAIRE

    Copin, Jean-Christophe; da Silva, Rafaela F.; Rodrigo A. Fraga-Silva; Capettini, Luciano; Quintao, Silvia; Lenglet, Sébastien; Pelli, Graziano; Galan, Katia; Burger, Fabienne; Braunersreuther, Vincent; Schaller, Karl; Deruaz, Maud; Proudfoot, Amanda E; Dallegri, Franco; Stergiopulos, Nikolaos

    2012-01-01

    Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) wa...

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

    Directory of Open Access Journals (Sweden)

    D. Thompson

    2017-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Shu XU

    2015-11-01

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

  9. Targeted Knockdown of Hepatic SOAT2 With Antisense Oligonucleotides Stabilizes Atherosclerotic Plaque in ApoB100-only LDLr-/- Mice.

    Science.gov (United States)

    Melchior, John T; Olson, John D; Kelley, Kathryn L; Wilson, Martha D; Sawyer, Janet K; Link, Kerry M; Rudel, Lawrence L

    2015-09-01

    To test the hypothesis that the attenuation of cholesterol oleate packaging into apoB-containing lipoproteins will arrest progression of pre-existing atherosclerotic lesions. Atherosclerosis was induced in apoB-100 only, LDLr(-/-) mice by feeding a diet enriched in cis-monounsaturated fatty acids for 24 weeks. A subset of mice was then euthanized to quantify the extent of atherosclerosis. The remaining mice were continued on the same diet (controls) or assigned to the following treatments for 16 weeks: (1) a diet enriched in n-3 polyunsaturated fatty acids, (2) the cis-monounsaturated fatty acid diet plus biweekly injections of an antisense oligonucleotide specific to hepatic sterol-O-acyltransferase 2 (SOAT2); or (3) the cis-monounsaturated fatty acid diet and biweekly injections of a nontargeting hepatic antisense oligonucleotide. Extent of atherosclerotic lesions in the aorta was monitored morphometrically in vivo with magnetic resonance imaging and ex vivo histologically and immunochemically. Hepatic knockdown of SOAT2 via antisense oligonucleotide treatment arrested lesion growth and stabilized lesions. Hepatic knockdown of SOAT2 in apoB100-only, LDLr(-/-) mice resulted in remodeling of aortic atherosclerotic lesions into a stable phenotype, suggesting SOAT2 is a viable target for the treatment of atherosclerosis. © 2015 American Heart Association, Inc.

  10. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.

    NARCIS (Netherlands)

    M. Naghavi (Morteza); P. Libby (Peter); E. Falk (Erling); S.W. Casscells (Ward); S. Litovsky (Silvio); J. Rumberger (John); J.J. Badimon; C. Stefanadis (Christodoulos); P.R. Moreno (Pedro); G. Pasterkamp (Gerard); Z. Fayad (Zahi); P.H. Stone (Peter); S. Waxman (Sergio); P. Raggi (Paolo); M. Madjid (Mohammad); A. Zarrabi (Alireza); A.E. Burke (Andrew); C. Yuan (Chun); P.J. Fitzgerald (Peter); D.S. Siscovick (David); C.L. de Korte (Chris); M. Aikawa (Masanori); K.E. Juhani Airaksinen; G. Assmann (Gerd); C.R. Becker (Christoph); J.H. Chesebro (James); A. Farb (Andrew); Z.S. Galis (Zorina); C. Jackson (Chris); I.-K. Jang (Il-Kyung); W. Koenig (Wolfgang); R.A. Lodder (Robert); K. March (Keith); J. Demirovic (Jasenka); M. Navab (Mohamad); S.G. Priori (Silvia); M.D. Rekhter (Mark); R. Bahr (Raymond); S.M. Grundy (Scott); R. Mehran (Roxana); A. Colombo (Antonio); E.A. Boerwinkle (Eric); C. Ballantyne (Christie); W. Insull Jr (William); R.S. Schwartz (Robert); R. Vogel (Robert); P.W.J.C. Serruys (Patrick); G.K. Hansson (Goran); D.P. Faxon (David); S. Kaul (Sanjay); H. Drexler (Helmut); P. Greenland (Philip); J.E. Muller (James); R. Virmani (Renu); P.M. Ridker (Paul); D.P. Zipes (Douglas); P.K. Shah (Prediman); J.T. Willerson (James)

    2003-01-01

    textabstractAtherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy di

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

    Directory of Open Access Journals (Sweden)

    Martin Andrassy

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  13. Positive remodeling index by MSCT coronary angiography: A prognostic factor for early detection of plaque rupture and vulnerability

    Directory of Open Access Journals (Sweden)

    Emad H. Abdeldayem

    2015-03-01

    Conclusion: Previous studies had shown that most acute coronary syndromes were initiated by sudden changes of mildly stenotic lesions, commonly found in positively remodeled vessels. Promising comparative results between MSCT and IVUS allowed consideration of MDCT as a useful tool in the noninvasive detection of potentially threatening coronary lesions. In our study, RI ⩾ 1.5 showed a strong correlation between the lipid plaque area, multiplicity of the plaques, and cross sectional area which were prognostic factors for plaque rupture and vulnerability, and thus, early detection of coronary artery disease. Modulation and prevention of positive remodeling by statin could promote to start medical treatment especially in cases where RI exceeds 1.5 and their follow up non-invasively by MDCT to detect reversal of remodeling and response of treatment.

  14. 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

    a correlation coefficient of r = -0.42 (p = 0.002), for mean echogenicity of the plaque region. The best performing feature was of second order and denoted Contrast (r = -0.5). Though significant, the latter correlation is probably not strong enough to be useful for clinical prediction of relative volume...

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

    Directory of Open Access Journals (Sweden)

    Clélia Le Gallic

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Human carotid atherosclerotic plaque protein(s) change HDL protein(s) composition and impair HDL anti-oxidant activity.

    Science.gov (United States)

    Cohen, Elad; Aviram, Michael; Khatib, Soliman; Volkova, Nina; Vaya, Jacob

    2016-01-01

    High density lipoprotein (HDL) anti-atherogenic functions are closely associated with cardiovascular disease risk factor, and are dictated by its composition, which is often affected by environmental factors. The present study investigates the effects of the human carotid plaque constituents on HDL composition and biological functions. To this end, human carotid plaques were homogenized and incubated with HDL. Results showed that after incubation, most of the apolipoprotein A1 (Apo A1) protein was released from the HDL, and HDL diameter increased by an average of approximately 2 nm. In parallel, HDL antioxidant activity was impaired. In response to homogenate treatment HDL could not prevent the accelerated oxidation of LDL caused by the homogenate. Boiling of the homogenate prior to its incubation with HDL abolished its effects on HDL composition changes. Moreover, tryptophan fluorescence quenching assay revealed an interaction between plaque component(s) and HDL, an interaction that was reduced by 50% upon using pre-boiled homogenate. These results led to hypothesize that plaque protein(s) interacted with HDL-associated Apo A1 and altered the HDL composition. Immuno-precipitation of Apo A1 that was released from the HDL after its incubation with the homogenate revealed a co-precipitation of three isomers of actin. However, beta-actin alone did not significantly affect the HDL composition, and yet the active protein within the plaque was elusive. In conclusion then, protein(s) in the homogenate interact with HDL protein(s), leading to release of Apo A1 from the HDL particle, a process that was associated with an increase in HDL diameter and with impaired HDL anti-oxidant activity.

  19. Pharmacological Treatment with Annexin A1 Reduces Atherosclerotic Plaque Burden in LDLR-/- Mice on Western Type Diet.

    Directory of Open Access Journals (Sweden)

    Dennis H M Kusters

    Full Text Available To investigate therapeutic effects of annexin A1 (anxA1 on atherogenesis in LDLR-/- mice.Human recombinant annexin A1 (hr-anxA1 was produced by a prokaryotic expression system, purified and analysed on phosphatidylserine (PS binding and formyl peptide receptor (FPR activation. Biodistribution of 99mTechnetium-hr-anxA1 was determined in C57Bl/6J mice. 12 Weeks old LDLR-/- mice were fed a Western Type Diet (WTD during 6 weeks (Group I or 12 weeks (Group P. Mice received hr-anxA1 (1 mg/kg or vehicle by intraperitoneal injection 3 times per week for a period of 6 weeks starting at start of WTD (Group I or 6 weeks after start of WTD (Group P. Total aortic plaque burden and phenotype were analyzed using immunohistochemistry.Hr-anxA1 bound PS in Ca2+-dependent manner and activated FPR2/ALX. It inhibited rolling and adherence of neutrophils but not monocytes on activated endothelial cells. Half lives of circulating 99mTc-hr-anxA1 were <10 minutes and approximately 6 hours for intravenously (IV and intraperitoneally (IP administered hr-anxA1, respectively. Pharmacological treatment with hr-anxA1 had no significant effect on initiation of plaque formation (-33%; P = 0.21(Group I but significantly attenuated progression of existing plaques of aortic arch and subclavian artery (plaque size -50%, P = 0.005; necrotic core size -76% P = 0.015, hr-anxA1 vs vehicle (Group P.Hr-anxA1 may offer pharmacological means to treat chronic atherogenesis by reducing FPR-2 dependent neutrophil rolling and adhesion to activated endothelial cells and by reducing total plaque inflammation.

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

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Awazu, Kunio

    2016-03-01

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

  1. Scan-Rescan Reproducibility of High Resolution Magnetic Resonance Imaging of Atherosclerotic Plaque in the Middle Cerebral Artery.

    Directory of Open Access Journals (Sweden)

    Xuefeng Zhang

    Full Text Available To evaluate the scan-rescan reproducibility of high-resolution magnetic resonance imaging (MRI of middle cerebral artery (MCA plaque, and calculate the number of subjects needed for future longitudinal clinical studies.Twenty two patients with MCA plaque were scanned twice by a T2-weighted fast-spin-echo sequence at 3T. Areas and volumes of MCA lumen, total vessel and plaque were quantified and compared between two repeated scans. Agreement and measurement error was quantified by intraclass correlation coefficient (ICC and coefficient of variance (CV as defined by standard deviation (SD of pair wise difference / mean. Sample size needed to detect 5% to 20% changes in area/volume was calculated using 80% power and 5% significance level.There was no significant different between the area and volume measurements of two repeated scans (p>0.05 with good agreement (ICC range 0.97-0.98 for area and 0.99 for volume. Relatively small measurement errors were observed with CVs range 6.1%-11.8% for area quantification and 4.9%-8.0% for volume quantification. Volume measurements tended to have 19.7% to 32.2% smaller CVs compared with area measurements. Sample size calculation showed a group of 47 patients was sufficient to detect 5% to 10% changes in MCA area/volume.High resolution MRI is feasible for quantifying intracranial plaque area and volume in longitudinal clinical studies with low scan-rescan variability. Volume measurement tends to be more reproducible compared with area measurements.

  2. Atherosclerotic plaque tissue characterization in 2D ultrasound longitudinal carotid scans for automated classification: a paradigm for stroke risk assessment.

    Science.gov (United States)

    Acharya, U Rajendra; Mookiah, Muthu Rama Krishnan; Vinitha Sree, S; Afonso, David; Sanches, Joao; Shafique, Shoaib; Nicolaides, Andrew; Pedro, L M; Fernandes E Fernandes, J; Suri, Jasjit S

    2013-05-01

    In the case of carotid atherosclerosis, to avoid unnecessary surgeries in asymptomatic patients, it is necessary to develop a technique to effectively differentiate symptomatic and asymptomatic plaques. In this paper, we have presented a data mining framework that characterizes the textural differences in these two classes using several grayscale features based on a novel combination of trace transform and fuzzy texture. The features extracted from the delineated plaque regions in B-mode ultrasound images were used to train several classifiers in order to prepare them for classification of new test plaques. Our CAD system was evaluated using two different databases consisting of 146 (44 symptomatic to 102 asymptomatic) and 346 (196 symptomatic and 150 asymptomatic) images. Both these databases differ in the way the ground truth was determined. We obtained classification accuracies of 93.1 and 85.3 %, respectively. The techniques are low cost, easily implementable, objective, and non-invasive. For more objective analysis, we have also developed novel integrated indices using a combination of significant features.

  3. Risk factor profiling and study of atherosclerotic coronary plaque burden and morphology with coronary computed tomography angiography in coronary artery disease among young Indians.

    Science.gov (United States)

    Chaudhary, R; Chauhan, A; Singhal, M; Bagga, S

    2017-08-01

    With a decade earlier manifestation of coronary artery disease (CAD) and paucity of data characterizing coronary plaque with coronary computed tomography angiography (CTA) among CAD patients in India, the study aimed to analyze patient characteristics and coronary plaque burden and morphology in young Indian patients with CAD. Serial coronary CTA was performed in 96 CAD patients. Among 60 patients ≤40years, risk factor and coronary plaque analysis done using a 256- slice CT in 33 patients with acute coronary syndrome (ACS) was compared with 27 patients with chronic stable angina (CSA). Univariate and multivariate analysis was performed, for factors predicting ACS as an outcome among young CAD patients. In addition, quantitative and morphologic plaque characteristics were compared among those ≤40years and >40years. Among 60 subjects ≤40years of age, 77% had dyslipidemia, 70% high lipoprotein(a), 53.33% elevated hs-CRP and 73.33% raised homocysteine. hs-CRP (9.33 vs. 3.33, p value=0.01) and serum triglycerides (178.67 vs. 141.42, p value=0.03) were markedly raised in patients with ACS. Statistically significant number of patients in the ACS group had positive remodelling (ACS, 69.7% vs. CSA, 14.8%; p value30mg/dL and composite vulnerability score maintained a predictive value for ACS in patients ≤40years. Statistically significant number of patients in the younger age group had higher mean total plaque volume (66.17±41.31mm(3) vs. 44.94±49.07mm(3); p=0.03), remodelling index (1.5±0.27 vs. 1.08±0.38; p=0.0001). Comparing culprit lesion characteristics of ACS patients in the two age groups, positive remodelling (95.8% vs. 70.5%, p=0.02), spotty calcification (50% vs. 11.7%, p=0.01) and non-calcified plaque (95.8% vs. 70.5%, p=0.02) were significantly more frequent in patients ≤40years. ACS in young Indians is characterized by a higher prevalence of both conventional and newer risk factors. In addition, culprit lesions in young ACS patients are more

  4. Serum ferritin is associated with carotid atherosclerotic plaques but not intima-media Thickness in patients with abnormal glucose metabolism.

    Science.gov (United States)

    Zhou, F L; Gao, Y; Tian, L; Yan, F F; Chen, T; Zhong, L; Tian, H M

    2015-10-23

    We investigated the association between serum ferritin and carotid artery lesions in populations with abnormal glucose metabolism. We included 70 participants with abnormal glucose metabolism and 170 participants with normal glucose metabolism and measured their baseline serum ferritin levels. During follow-up carotid intima-media thickness and carotid plaque were evaluated. Serum ferritin levels were higher in the participants with abnormal glucose metabolism (pferritin was excluded from the final equation in the logistic regression. Furthermore, age, waist circumference, ferritin, 2h-PG, and total cholesterol were significantly different between the subgroups with and without carotid plaque. When the above data were included in a logistic regression model, the p values obtained for age, ferritin, and 2h-PG were 0.004, 0.032, and 0.011, respectively. In the Chinese population, serum ferritin levels are significantly increased in patients with abnormal glucose metabolism. The carotid intima-media thickness showed no independent relationship with serum ferritin in patients with abnormal glucose metabolism. However, high serum ferritin is an important risk factor for carotid atherosclerosis in these patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques

    DEFF Research Database (Denmark)

    Tuenter, A.; Selwaness, M.; Arias Lorza, A.

    2016-01-01

    BACKGROUND AND AIMS: Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque...... estimating equations analysis, adjusting for age, sex and carotid wall thickness. RESULTS: The study group consisted of 93 atherosclerotic carotid arteries of 74 participants. In plaques with higher maximum shear stresses, IPH was more often present (OR per unit increase in maximum shear stress (log...... formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons. METHODS: Participants (n = 74) from the population-based Rotterdam...

  6. 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.

  7. Differential effects of Nd-YAG laser on collagen and elastin production by chick embryo aortae in vitro. Relevance to laser angioplasty for removal of atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Abergel, R.P.; Zaragoza, E.J.; Dwyer, R.M.; Uitto, J.

    1985-08-30

    Aortae from 17-day old chick embryos were subjected to irradiation with a Nd:YAG laser at energy densities varying from 1.2 - 4.7 X 10(3) J/cm2. The aortae were pulse-labeled in vitro with (/sup 3/H)proline or (/sup 14/C)valine, and the synthesis of collagenous polypeptides and soluble elastin was examined by SDS-polyacrylamide gel electrophoresis, followed by fluorography and quantitative scanning densitometry. Irradiation of the aortae with Nd:YAG laser resulted in inhibition of the synthesis of the extracellular matrix proteins. The production of collagen was inhibited to a considerably larger degree than the production of elastin. Thus, the biosynthetic pathway for collagen production appears to be more susceptible to laser inhibition than the corresponding pathway for elastin production. These observations may have relevance to laser angioplasty which has been proposed to be applicable for removal of atherosclerotic plaques in human vessels. Specifically, the results suggest that inhibition of the extracellular matrix production may result in weakening of the vessel wall with subsequent aneurysm formation and rupture.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. The culture and detection of nanobacteria in abdominal aorta atherosclerotic plaque%腹主动脉粥样硬化斑块中纳米细菌的培养与鉴定

    Institute of Scientific and Technical Information of China (English)

    耿文茂; 张倩; 吴亚光; 秦成坤; 苏忠学

    2012-01-01

    目的 观察腹主动脉粥样硬化斑块中是否存在纳米细菌,并对其进行鉴定.方法 12例腹主动脉粥样硬化斑块及12例正常动脉血管组织研磨,取上清液培养.8周后收集培养瓶底白色粉末,用纳米细菌单克隆抗体间接免疫荧光法对其进行检测,并利用电镜进一步观察.结果 12例动脉粥样硬化斑块中10例纳米细菌检测阳性,2例阴性,12例正常动脉血管组织中1例纳米细菌检测阳性,11例阴性,差异有统计学意义(P<0.05).纳米细菌单克隆抗体间接免疫荧光检测时可发出绿色荧光,电镜下测量纳米细菌直径约为100 ~ 300 nm.结论 腹主动脉粥样硬化斑块中存在纳米细菌,它可能导致粥样硬化斑块不稳定.%Objective To investigate whether the nanobacteria exists in abdominal aorta atherosclerotic plaque or not and detect it.Methods 12 case of abdominal aorta atherosclerotic plaques and 12 case of normal artery were grinded,the supematant fluid was cultured for eight weeks.Subsequently,the white extract from the culture flask was detected by nanobacteria monoclonal antibody immunofluorescence and electron microscope.Results Nanobacteria was positive in 10 case of atherosclerotic plaques but only in 1 case of normal artery,the difference was statistically significant (P < 0.05).Green fluorescence could be present during indirect immunofluorescence detection.The size of nanobacreria was measured ranging from 100nm to 300nm by electron microscope analysis.Conclusion Nanobacteria was detected in abdominal aorta atherosclerotic plaques and might led to atherosclerotic plaques instability.

  12. Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques.

    Science.gov (United States)

    Packard, René R Sevag; Zhang, XiaoXiao; Luo, Yuan; Ma, Teng; Jen, Nelson; Ma, Jianguo; Demer, Linda L; Zhou, Qifa; Sayre, James W; Li, Rongsong; Tai, Yu-Chong; Hsiai, Tzung K

    2016-09-01

    Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 µm in diameter and separated by 400 µm was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy.

  13. Plaque rupture in humans and mice

    DEFF Research Database (Denmark)

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

    2007-01-01

    Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms...... such as "instability", "vulnerable", "rupture", or even "thrombosis" for features of plaques in murine model systems not yet shown to rupture spontaneously and in an animal surprisingly resistant to formation of thrombi at sites of atherosclerosis. We suggest that use of conclusory terms like "vulnerable" and "stable...... that various forms of data have implicated in plaque progression. For example, formation of the fibrous cap, protease activation, and cell death in the necrotic core can be well described and have all been modeled in well-defined experiments. The relevance of such well-defined, objective, descriptive...

  14. Xiaoxianggou attenuates atherosclerotic plaque formation in endogenous high Ang II ApoE(-/-) mice via the inhibition of miR-203 on the expression of Ets-2 in endothelial cells.

    Science.gov (United States)

    Nie, Wencheng; Zhang, Xiaoqun; Yan, Hui; Li, Shan; Zhu, Weiguo; Fan, Fangyan; Zhu, Jianhua

    2016-08-01

    Atherosclerosis is a chronic immune-inflammatory disorder and one of the leading causes responsible for cardiovascular morbidity and mortality. Traditional Chinese medicine treatment with multi-targets has shown prospects for the therapeutic effect on atherosclerosis. Thus, this study aims to investigate whether xiaoxianggou has benefit for reducing the atherosclerotic plaque area in endogenous high Ang II ApoE(-/-) mice and investigated the underlying mechanisms. Endogenous high Ang II ApoE(-/-) mice model was generated by using two kidney one clip (2K1C). All mice were treated by intragastric administration with xiaoxianggou two times a week for 16 weeks. En face plaque area was analyzed by oil-red O staining. Serum anti-OxLDL antibodies were measured by ELISA assay. Expression of miR-203 and Ets-2 were evaluated using qRT-RCR and western blotting analysis, respectively. This study revealed that xiaoxianggou treatment dose-dependently reduced the atherosclerotic plaque area and serum autoantibodies against oxLDL, elevated miR-203 expression and reduced Ets-2 expression in endogenous high Ang II ApoE(-/-) mice. In primary arterial ECs, Xiaoxianggou reverses the reduced miR-203 expression and the elevated Ets-2 expression induced by AngII, which was further recovered by miR-203 inhibitor. Additionally, miR-203 regulated the expression of Ets-2 by targeting Ets-2-3' UTR. Moreover, miR-203 inhibitor reversed the reduction of atherosclerotic lesion area induced by Xiaoxianggou. These findings present that xiaoxianggou plays an anti-atherosclerotic role in endogenous high Ang II ApoE(-/-) mice model, which is partly due to its antioxidant actions against atherosclerosis and the inhibition of miR-203 on the expression of Ets-2 in endothelial cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Preclinical models of atherosclerosis. The future of Hybrid PET/MR technology for the early detection of vulnerable plaque.

    Science.gov (United States)

    Cuadrado, Irene; Saura, Marta; Castejón, Borja; Martin, Ana María; Herruzo, Irene; Balatsos, Nikolaos; Zamorano, Jose Luis; Zaragoza, Carlos

    2016-04-08

    Cardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new non-invasive imaging technologies, they have become essential tools to evaluate new therapeutic strategies, with which can forecast and prevent plaque rupture. Positron emission tomography (PET)/computed tomography imaging is currently used for plaque visualisation in clinical and pre-clinical cardiovascular research, albeit with significant limitations. However, the combination of PET and magnetic resonance imaging (MRI) technologies is still the best option available today, as combined PET/MRI scans provide simultaneous data acquisition together with high quality anatomical information, sensitivity and lower radiation exposure for the patient. The coming years may represent a new era for the implementation of PET/MRI in clinical practice, but first, clinically efficient attenuation correction algorithms and research towards multimodal reagents and safety issues should be validated at the preclinical level.

  16. The expanding indications for virtual histology intravascular ultrasound for plaque analysis prior to carotid stenting.

    Science.gov (United States)

    Schiro, B J; Wholey, M H

    2008-12-01

    Complications of carotid artery stenting (CAS), including stroke, remain relatively high when compared with carotid endarterectomy (CEA). Current selection criteria for patients undergoing CAS are based predominately on surgical risk related to other comorbidities. Little attention is given to the morphology of the atherosclerotic plaque, although studies have shown that extensive variability exists which confers certain risks for plaque vulnerability. Virtual Histology intravascular ultrasound (VH IVUS) offers a unique method of assessing plaque morphology prior to CAS. Herein, the authors review the concepts of atherosclerotic plaque morphology and discuss the background of VH IVUS and illustrate its use in the carotid system. With selection of the appropriate patient and the appropriate plaque, more favorable outcomes of CAS may be achieved which will solidify its place as a frontline treatment of carotid vascular disease.

  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. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

  19. Quantitative and qualitative estimation of atherosclerotic plaque burden in vivo at 7T MRI using Gadospin F in comparison to en face preparation evaluated in ApoE KO mice.

    Science.gov (United States)

    Jung, Caroline; Christiansen, Sabine; Kaul, Michael Gerhard; Koziolek, Eva; Reimer, Rudolph; Heeren, Jörg; Adam, Gerhard; Heine, Markus; Ittrich, Harald

    2017-01-01

    The aim of the study was to quantify atherosclerotic plaque burden by volumetric assessment and T1 relaxivity measurement at 7T MRI using Gadospin F (GDF) in comparison to en face based measurements. 9-weeks old ApoE-/- (n = 5 for each group) and wildtype mice (n = 5) were set on high fat diet (HFD). Progression group received MRI at 9, 13, 17 and 21 weeks after HFD initiation. Regression group was reswitched to chow diet (CD) after 13 weeks HFD and monitored with MRI for 12 weeks. MRI was performed before and two hours after iv injection of GDF (100 μmol/kg) at 7T (Clinscan, Bruker) acquiring a 3D inversion recovery gradient echo sequence and T1 Mapping using Saturation Recovery sequences. Subsequently, aortas were prepared for en face analysis using confocal microscopy. Total plaque volume (TPV) and T1 relaxivity were estimated using ImageJ (V. 1.44p, NIH, USA). 2D and 3D en face analysis showed a strong and exponential increase of plaque burden over time, while plaque burden in regression group was less pronounced. Correspondent in vivo MRI measurements revealed a more linear increase of TPV and T1 relaxivity for regression group. A significant correlation was observed between 2D and 3D en face analysis (r = 0.79; p<0.001) as well as between 2D / 3D en face analysis and MRI (r = 0.79; p<0.001; r = 0.85; p<0.001) and delta R1 (r = 0.79; p<0.001; r = 0.69; p<0.01). GDF-enhanced in vivo MRI is a powerful non-invasive imaging technique in mice allowing for reliable estimation of atherosclerotic plaque burden, monitoring of disease progression and regression in preclinical studies.

  20. Molecular imaging of plaques in coronary arteries with PET and SPECT

    Institute of Scientific and Technical Information of China (English)

    Zhong-Hua SUN; Hairil Rashmizal; Lei XU

    2014-01-01

    Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lu-men stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increas-ingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography (PET) and single photon emission computed tomography (SPECT) has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging tech-niques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coro-nary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.

  1. 剪切波弹性成像用于动脉粥样斑块组织成分定征及易损性评价的实验研究%Characterization of atherosclerotic plaque components and identification of vulnerablity by shear wave elastography:in vivo study on a rabbit model

    Institute of Scientific and Technical Information of China (English)

    樊荣; 冯建钦; 郭倩倩; 张梅; 张运; 张鹏飞

    2015-01-01

    Objective To investigate the value of shear wave elastography (SWE)on characterizing components and identifying the vulnerability of atherosclerotic plaques in vivo on a rabbit model.Methods The accuracy,as well as the inter-and intra-observer variance of quantifying the Young's modulus by SWE technique was first evaluated with the CIRS� phantoms as the golden standard.Animal model was developed by abdominal aorta endothelium denudation and high-cholesterol diet for 24 weeks on 20 purebred New Zealand rabbits.SWE images of atherosclerotic plaques found in the abdominal aortas were acquired in situ to acquire the Young's modulus.Then the plaques were harvested and matched with the distance between the right renal artery and the plaques recorded during SWE imaging.Histological slices were stained for fat,collagen,smooth muscle cells (SMC)and macrophages by Oil O red,picric Sirius red and anti-α-SMC,anti-RAM-1 1 immunohistology.Vulnerability index was also calculated as the percentage of (macrophage+fat)/(smooth muscle cell+collagen ).The correlation between the Young's modulus and plaque components and vulnerability index was analyzed.The value of SWE on differentiating plaque types was evaluated by ROC analysis.Results High agreement was found between the estimated Young's modulus by SWE and the gold standard.The coefficient of variant of inter-and intra-observer was very low at the range of 1.0%-3.8%.Ten fatty and twenty fibro-fatty plaques were obtained,totally.The maximal and mean Young's moduli of the fatty plaque were (49.90±22.95)kPa and (40.15±22.60)kPa,which were lower than those of the fibro-fatty plaques [(88.49±37.27)kPa and (72.93±29.21)kPa,respectively].The maximal Young's modulus obtained by SWE correlated positively with collagen and SMC (r =0.567 and 0.561,respectively with P <0.001),and negatively with fat and macrophage infiltration (r =-0.542 and-00.482,respectively with P <0.005).The mean Young's modulus also correlated positively with

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

    Institute of Scientific and Technical Information of China (English)

    戴志刚; 王涛; 武文元

    2011-01-01

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

  3. 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.

    Science.gov (United States)

    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

    2010-10-01

    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 inversion-recovery fast spin echo is limited. Study aims were: evaluation of (1) timing of MRI after intravenous injection of cannabinoid-2 receptor (CB2-R) (expressed by human and mouse plaque macrophages) targeted micelles; (2) inter-scan variability of inversion-recovery fast spin echo and fast spin echo; (3) relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo and fast spin echo. Inversion-recovery fast spin echo/fast spin echo imaging was performed before and every 15 min up to 48 h after injection of CB2-R targeted or control micelles using several groups of mice measured in an interleaved fashion. NER(plaque) (determined on inversion-recovery fast spin echo images) remained high (∼2) until 48 h after injection of CB2-R targeted micelles, whereas NER(plaque) decreased after 36 h in the control group. The inter-scan variability and relation between NER(plaque) and gadolinium (assessed with inductively coupled plasma- mass spectrometry) were compared between inversion-recovery fast spin echo and fast spin echo. Inter-scan variability was higher for inversion-recovery fast spin echo than for fast spin echo. Although gadolinium and NER(plaque) correlated well for both techniques, the NER of plaque was higher for inversion-recovery fast spin echo than for fast spin echo. In mice injected with CB2-R targeted micelles, NER(plaque) can be best evaluated at 36-48 h post-injection. Because NER(plaque) was higher for inversion-recovery fast spin echo than for fast spin echo, but with high inter-scan variability, repeated inversion-recovery fast spin echo imaging and averaging of the obtained NER(plaque) values is recommended.

  4. Mucosal tolerance to a combination of ApoB and HSP60 peptides controls plaque progression and stabilizes vulnerable plaque in Apob(tm2SgyLdlr(tm1Her/J mice.

    Directory of Open Access Journals (Sweden)

    Lakshmi Mundkur

    Full Text Available Oral tolerance to auto antigens reduces the development of atherosclerosis in mouse models. However, the effect of immune tolerance to multiple self antigenic peptides in plaque progression and stabilization is not known. We studied the protective effect of mucosal tolerance to peptides from apolipoprotein B (ApoB; 661-680 and heat shock protein 60 (HSP60; 153-163, in combination with diet, in the prevention of atherosclerotic lesion progression and plaque stabilization in ApoB(tm25gyLDLr(tm1Her mice. We found that oral administration of five doses of a combination of ApoB and HSP60 peptides (20 µg/mice/dose induced tolerance to both the peptides and reduced early plaque development by 39.9% better than the individual peptides (ApoB = 28.7%;HSP60 = 26.8%(P<0.001. Oral tolerance to combination of peptides along with diet modification arrested plaque progression by 37.6% which was associated with increases in T-regulatory cell and transforming growth factor-β expression in the plaque and peripheral circulation. Reduced macrophage infiltration and tumor necrosis factor-α expression in the plaque was also observed. Tolerance with continued hypercholesterolemia resulted in 60.8% reduction in necrotic core area suggesting plaque stabilization, which was supported by reduction in apoptosis and increased efferocytosis demonstrated by greater expression of receptor tyrosine kinase Mer (MerTK in the plaque. Tolerance to the two peptides also reduced the expression of matrix metalloproteinase 9, tissue factor, calprotectin, and increased its collagen content. Our study suggests that oral tolerance to ApoB and HSP60 peptide combination induces CD4(+ CTLA4(+ Tregs and CD4(+CD25(+Foxp3(+ Tregs secreting TGF-β, which inhibit pathogenic T cell response to both peptides thus reducing the development and progression of atherosclerosis and provides evidence for plaque stabilization in ApoB(tm25gyLDLr(tm1Her mice.

  5. Three-dimensional modeling of oxidized-LDL accumulation and HDL mass transport in a coronary artery: a proof-of-concept study for predicting the region of atherosclerotic plaque development.

    Science.gov (United States)

    Sakellarios, Antonis I; Siogkas, Panagiotis K; Athanasiou, Lambros S; Exarchos, Themis P; Papafaklis, Michail I; Bourantas, Christos V; Naka, Katerina K; Michalis, Lampros K; Filipovic, Nenad; Parodi, Oberdan; Fotiadis, Dimitrios I

    2013-01-01

    Low density lipoprotein (LDL) has a significant role on the atherosclerotic plaque development, while the concentration of high density lipoproteins (HDL) is considered to play an atheroprotective role according to several biochemical mechanisms. In this work, it is the first time that both LDL and HDL concentrations are taken into account in order to predict the regions prone for plaque development. Our modeling approach is based on the use of a realistic three-dimensional reconstructed pig coronary artery in two time points. Biochemical data measured in the pig were also included in order to develop a more customized model. We modeled coronary blood flow by solving the Navier-Stokes equations in the arterial lumen and plasma filtration in the arterial wall using Darcy's Law. HDL transport was modeled only in the arterial lumen using the convection-diffusion equation, while LDL transport was modeled both in the lumen and the arterial wall. An additional novelty of this work is that we model the oxidation of LDL taking into account the atheroprotective role of HDL. The results of our model were in good agreement with histological findings demonstrating that increased oxidized LDL is found near regions of advanced plaques, while non-oxidized LDL is found in regions of early plaque types.

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

    Directory of Open Access Journals (Sweden)

    Amir H. Najafi

    2013-03-01

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

  7. An analysis on the Risk Factors of Carotid Artery Atherosclerotic Plaques in Cerebral Infarction Patients%脑梗死患者颈动脉粥样硬化斑块的相关因素分析

    Institute of Scientific and Technical Information of China (English)

    王本孝; 许平

    2011-01-01

    Objective:To explore the risk factors for carotid artery atherosclerotic plaques in cerebral infarction patients. Methods: Color doppler ultrasound scanner was used to detect the plaques of the carotid arteries in patients with cerebral infarction (n=126) and normal controls (n=61). According to the doppler ultrasound scanning, the patients were divided into plaque (+) group (n=102) and plaque(—) group (n=24). The patients in the plaque(+) group were further divided into stable plaque (n=35) and unstable plaque subgroups (n=67). The physical data and the concentration of total cholesterol(TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA),apolipoprotein B (ApoB), lipoprotein-a (Lp(a)), fibrinogen (FIB) and blood glucose (BG) were measured, and compared between the groups. Results: Carotid atherosclerotic artery plaques were detected in 80.9% of the patients, which was significantly higher than that in the normal controls (P<0.01). When compared with those in plaque(—) group, those patients were much older. Smoking, hypertension, diabetes, higher concentrations of TC, Lp(a), ApoB, FIB, LDLC, and BG were more frequently found in the plaque(+) group. The FIB concentrations of patients in the unstable plaque subgroup was much higher that in the stable plaque subgroup (P<0.05). Conclusion: Carotid atherosclerotic plaques were the risk factor for cerebral infarction.Old age, smoking, hypertention, diabetes mellitus, lipoidosis, and high fibrinogen are the risk factors for carotid atherosclerotic plaques. High concentration of fibrinogen affects stability of the plaques.%目的:探讨脑梗死患者颈动脉粥样硬化斑块形成及其稳定性的相关影响因素.方法:应用彩色多普勒超声检测脑梗死患者126例及正常对照者61例颈动脉斑块形成情况;根据超声检查结果将126例脑梗死患者分为有斑块组102

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  10. Relationship between glycemic control and coronary artery disease severity, prevalence and plaque characteristics by computed tomography coronary angiography in asymptomatic type 2 diabetic patients.

    Science.gov (United States)

    Tavares, C A F; Rassi, C H R E; Fahel, M G; Wajchenberg, B L; Rochitte, C E; Lerario, A C

    2016-10-01

    Evaluate whether glycemic control in type 2 diabetes (DM2) asymptomatic for coronary artery disease (CAD) affects not only the presence and magnitude of CAD but also the characteristics of plaque vulnerability using multidetector row computed coronary tomography (MDCT). Acute coronary syndrome (ACS) is frequently observed in asymptomatic DM2 patients. Positive vessel remodeling (PR) and low-attenuation plaques (LAP) identified by MDCT have been demonstrated to be characteristics of subsequent culprit lesions of ACS. However, little is known regarding plaque characteristics in asymptomatic diabetic patients and their relationship with glycemic control. Ninety asymptomatic DM2 patients, aged 40-65 years old, underwent MDCT. The presence of atherosclerotic obstruction, defined as coronary stenosis ≥50 %, and plaque characteristics were compared between two groups of patients with A1c patients, 38 (42.2 %) presented with coronary atherosclerotic plaques, 11 had A1c patients had significant lumen obstruction higher than 50 %: 3 in the A1c patients, the simultaneous presence of two vulnerability plaque characteristics (PR and LAP) were observed more frequently in the A1c ≥ 7 group (n = 8) than in the A1c patients with A1c ≥ 7 % have a higher frequency of CAD and a higher proportion of vulnerable atherosclerotic coronary plaque by MDCT compared to patients with DM2 with A1c < 7 in our study.

  11. The Distribution of Macrophages and the Mechanism of Macrophages Accumulation in Atheroscle-rotic Plaques%动脉粥样硬化斑块中巨噬细胞的分布与蓄积机制

    Institute of Scientific and Technical Information of China (English)

    王林青; 李全忠; 钱宗杰

    2016-01-01

    动脉粥样硬化斑块破裂可导致严重的临床事件(如心肌梗死和脑卒中)。巨噬细胞是动脉粥样硬化斑块内最主要的炎性细胞,它可根据不同的微环境分化成不同表型的巨噬细胞。其中, M1型巨噬细胞主要位于斑块不稳定区,M2型巨噬细胞主要位于斑块的稳定区。随着动脉粥样硬化斑块的进展,斑块内积聚的巨噬细胞逐渐增多,而斑块内不断蓄积的巨噬细胞主要依赖于局部巨噬细胞的增殖,而不是血中单核细胞的分化。%The rupture of atherosclerotic plaque can lead to severe consequences, such as myocardial infraction and stroke.Macrophages are the predominant inflammatory cells within the plaques,which are very versatile and can polarize different phenotypes depending on the local microenvironment .M1 macrophages are exclusively found in unstable plaques and M2 macrophages being higher in stable plaques.The incremental accumulation of macrophages corresponded with plaque progression,are mainly derived from local prolifera-tion rather than from the influx of blood-borne monocytes.

  12. Reproducibility of coronary atherosclerotic plaque characteristics in populations with low, intermediate, and high prevalence of coronary artery disease by multidetector computer tomography: a guide to reliable visual coronary plaque assessments.

    Science.gov (United States)

    de Knegt, Martina C; Linde, Jesper J; Fuchs, Andreas; Nordestgaard, Børge G; Køber, Lars V; Hove, Jens D; Kofoed, Klaus F

    2016-10-01

    To evaluate the interobserver agreement of visual coronary plaque characteristics by 320-slice multidetector computed tomography (MDCT) in three populations with low, intermediate and high CAD prevalence and to identify determinants for the reproducible assessment of these plaque characteristics. 150 patients, 50 asymptomatic subjects from the general population (low CAD prevalence), 50 symptomatic non-acute coronary syndrome (non-ACS) patients (intermediate CAD prevalence), and 50 ACS patients (high CAD prevalence), matched according to age and gender, were retrospectively enrolled. All coronary segments were evaluated for overall image quality, evaluability, presence of CAD, coronary stenosis, plaque composition, plaque focality, and spotty calcification by four readers. Interobserver agreement was assessed using Fleiss' Kappa (κ) and intra-class correlation (ICC). Widely used clinical parameters (overall scan quality, presence of CAD, and determination of coronary stenosis) showed good agreement among the four readers, (ICC = 0.66, κ = 0.73, ICC = 0.74, respectively). When accounting for heart rate, body mass index, plaque location, and coronary stenosis above/below 50 %, interobserver agreement for plaque composition, presence of CAD, and coronary stenosis improved to either good or excellent, (κ = 0.61, κ = 0.81, ICC = 0.78, respectively). Spotty calcification was the least reproducible parameter investigated (κ = 0.33). Across subpopulations, reproducibility of coronary plaque characteristics generally decreased with increasing CAD prevalence except for plaque composition, (limits of agreement: ±2.03, ±1.96, ±1.79 for low, intermediate and high CAD prevalence, respectively). 320-slice MDCT can be used to assess coronary plaque characteristics, except for spotty calcification. Reproducibility estimates are influenced by heart rate, body size, plaque location, and degree of luminal stenosis.

  13. Morphological and Stress Vulnerability Indices for Human Coronary Plaques and Their Correlations with Cap Thickness and Lipid Percent: An IVUS-Based Fluid-Structure Interaction Multi-patient Study.

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2015-12-01

    Full Text Available Plaque vulnerability, defined as the likelihood that a plaque would rupture, is difficult to quantify due to lack of in vivo plaque rupture data. Morphological and stress-based plaque vulnerability indices were introduced as alternatives to obtain quantitative vulnerability assessment. Correlations between these indices and key plaque features were investigated. In vivo intravascular ultrasound (IVUS data were acquired from 14 patients and IVUS-based 3D fluid-structure interaction (FSI coronary plaque models with cyclic bending were constructed to obtain plaque wall stress/strain and flow shear stress for analysis. For the 617 slices from the 14 patients, lipid percentage, min cap thickness, critical plaque wall stress (CPWS, strain (CPWSn and flow shear stress (CFSS were recorded, and cap index, lipid index and morphological index were assigned to each slice using methods consistent with American Heart Association (AHA plaque classification schemes. A stress index was introduced based on CPWS. Linear Mixed-Effects (LME models were used to analyze the correlations between the mechanical and morphological indices and key morphological factors associated with plaque rupture. Our results indicated that for all 617 slices, CPWS correlated with min cap thickness, cap index, morphological index with r = -0.6414, 0.7852, and 0.7411 respectively (p<0.0001. The correlation between CPWS and lipid percentage, lipid index were weaker (r = 0.2445, r = 0.2338, p<0.0001. Stress index correlated with cap index, lipid index, morphological index positively with r = 0.8185, 0.3067, and 0.7715, respectively, all with p<0.0001. For all 617 slices, the stress index has 66.77% agreement with morphological index. Morphological and stress indices may serve as quantitative plaque vulnerability assessment supported by their strong correlations with morphological features associated with plaque rupture. Differences between the two indices may lead to better plaque

  14. Reproducibility of coronary atherosclerotic plaque characteristics in populations with low, intermediate, and high prevalence of coronary artery disease by multidetector computer tomography

    DEFF Research Database (Denmark)

    de Knegt, Martina C; Linde, Jesper J; Fuchs, Andreas

    2016-01-01

    To evaluate the interobserver agreement of visual coronary plaque characteristics by 320-slice multidetector computed tomography (MDCT) in three populations with low, intermediate and high CAD prevalence and to identify determinants for the reproducible assessment of these plaque characteristics....... 150 patients, 50 asymptomatic subjects from the general population (low CAD prevalence), 50 symptomatic non-acute coronary syndrome (non-ACS) patients (intermediate CAD prevalence), and 50 ACS patients (high CAD prevalence), matched according to age and gender, were retrospectively enrolled. All...

  15. 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.)

  16. Three-Dimensional Carotid Plaque Progression Simulation Using Meshless Generalized Finite Difference Method Based on Multi-Year MRI Patient-Tracking Data.

    Science.gov (United States)

    Yang, Chun; Tang, Dalin; Atluri, Satya

    2010-01-01

    Cardiovascular disease (CVD) is becoming the number one cause of death worldwide. Atherosclerotic plaque rupture and progression are closely related to most severe cardiovascular syndromes such as heart attack and stroke. Mechanisms governing plaque rupture and progression are not well understood. A computational procedure based on three-dimensional meshless generalized finite difference (MGFD) method and serial magnetic resonance imaging (MRI) data was introduced to quantify patient-specific carotid atherosclerotic plaque growth functions and simulate plaque progression. Participating patients were scanned three times (T1, T2, and T3, at intervals of about 18 months) to obtain plaque progression data. Vessel wall thickness (WT) changes were used as the measure for plaque progression. Since there was insufficient data with the current technology to quantify individual plaque component growth, the whole plaque was assumed to be uniform, homogeneous, isotropic, linear, and nearly incompressible. The linear elastic model was used. The 3D plaque model was discretized and solved using a meshless generalized finite difference (GFD) method. Four growth functions with different combinations of wall thickness, stress, and neighboring point terms were introduced to predict future plaque growth based on previous time point data. Starting from the T2 plaque geometry, plaque progression was simulated by solving the solid model and adjusting wall thickness using plaque growth functions iteratively until T3 is reached. Numerically simulated plaque progression agreed very well with the target T3 plaque geometry with errors ranging from 11.56%, 6.39%, 8.24%, to 4.45%, given by the four growth functions. We believe this is the first time 3D plaque progression simulation based on multi-year patient-tracking data was reported. Serial MRI-based progression simulation adds time dimension to plaque vulnerability assessment and will improve prediction accuracy for potential plaque rupture

  17. 血脂指标比值对颈动脉粥样斑块预测价值的比较%Comparison of the Value of Serum Lipids Index Ratio in the Prediction of Carotid Atherosclerotic Plaques

    Institute of Scientific and Technical Information of China (English)

    宋川; 郑延松; 王丽凤; 陈志来; 郭民法

    2012-01-01

    目的 探讨总胆固醇与高密度脂蛋白胆固醇(TC/HDL-C)比值和低密度脂蛋白胆固醇/高密度脂蛋白胆固醇(LDL-C/HDL-C)比值对颈动脉粥样斑块的预测价值.方法 选取2010年5月-2011年10月在我院健康医学中心进行健康体检并接受颈部血管超声检查和血脂检测的4 282例体检者作为研究对象,对颈动脉粥样斑块与相关因素[年龄、性别、教育程度、吸烟、饮酒、腰围、体质指数、血压和血糖、血红蛋白、血尿酸、TC、三酰甘油(TG)、LDL-C、HDL-C、超敏C反应蛋白水平及糖尿病、高血压、冠心病、脑卒中家族史]进行分析.结果 4 282例体检者中1 438例(33.6%)存在颈动脉粥样斑块,2 844例(66.4%)未发现明显的颈动脉粥样斑块.年龄、性别、吸烟、血糖、收缩压、LDL-C、HDL-C、超敏C反应蛋白均为颈动脉粥样斑块的危险因素.若用LDL-C/HDL-C和TC/HDL-C分别替代LDL-C、HDL-C或者TC和HDL-C,LDL-C/HDL-C和TC/HDL-C比值仍为颈动脉粥样斑块的危险因素.与TC/HDL-C比值(β=0.1760)相比,LDL-C/HDL-C比值的偏回归系数(β=0.3292)更高.结论 当用于预测颈动脉粥样斑块时,LDL-C/HDL-C比值比TC/HDL-C比值更具临床使用价值.%Objective To explore the value of the ratio of TC to HDL - C and the ratio of LDL - C to HDL - C ( LDL - C/HDL - C ) in the prediction of carotid atherosclerotic plaques. Methods 4 282 subjects registered for health examination and underwent carotid Doppler ultrasound scan and serum lipids test in the department of health science center in our hospital from May 2010 to October 2011 were involved into the study. Carotid atherosclerotic plaques and related factors ( age, gender, education, smoking status, alcohol intake, waist circumference, body mass index, blood pressure, blood glucose, hemoglobin, blood uric acid, TC, TG, LDL - C, HDL - C, hs - CRP, diabetes, hypertension, coronary heart disease and family history of stroke ) were analyzed. Results

  18. 兔颈动脉粥样硬化斑块内MMP-2与新生血管关系的研究%The relationship between MMP-2 and the neovascularization in rabbit carotid atherosclerotic plaque

    Institute of Scientific and Technical Information of China (English)

    樊建华

    2011-01-01

    To detect the relationship between matrix metaloproteinase -2 (MMP -2) and the neova - scularization in rabbit carotid atherosclerotic model plaque, forty of the male New Zealand white rabbits were randomly divided into 4 groups: group A (the blank control group), group B (high-cholesterol diet group), group C (silicone collar intervention and high-cholesterol diet for 14 days group), group D (silicone collar intervention and high -cholesterol diet for 28 days group). We used contrast -enhanced ultrasound (CEUS) to detect the neovascularization in the carotid atherosclerosis plaque. The expressions of MMP-2 and cluster of differentiation 31 (CD31) were assessed by immunohistochemical staining, and we analyzed the correlations between them. CEUS showed that the neovascularization in the carotid atherosclerotic model plaques was statistical difference between the C and D group (P < 0.05); immunohistochemistry showed there were positive MMP-2 and CD31 expressions in the plaques, and the correlative analysis showed the expressions were positive correlated (P < 0.01). We can conclude that MMP-2 play some roles in the neovascularization within the rabbit carotid atherosclerotic plaques.%目的 探讨兔颈动脉粥样硬化模型斑块内基质金属蛋白酶-2(matrix metaloproteinase-2,MMP-2)与新生血管的关系.方法 将40只健康雄性新西兰大白兔随机分为4组,A组予普通饲料喂养28 d、B组予高脂饮食28 d、C组予硅橡胶圈干预联合高脂饮食14d、D组予硅橡胶圈干预联合高脂饮食28 d.利用超声造影检测C组、D组兔颈动脉粥样硬化模型斑块内新生血管情况,应用免疫组化检测斑块内MMP-2、血小板内皮细胞黏附分子-1(cluster of differentiation 31,CD31)的表达,进行两者间相关性分析.结果 超声造影检测到C组、D组模型兔颈动脉斑块内有新生血管形成,两组间差异有统计学意义(P<0.05).免疫组化结果显示斑块内有阳性表达的MMP-2、CD31,

  19. The Study on the Factors of the Formation of Carotid Atherosclerotic Plaque%颈动脉粥样硬化斑块形成的相关因素分析

    Institute of Scientific and Technical Information of China (English)

    邓珊; 佘军红; 翁保慧; 阳洪

    2011-01-01

    目的 探讨颈动脉斑块形成的主要相关因素,以指导临床进行缺血性脑卒中的预防.方法 选择2010年12月至2011年3月期间在广西医科大学第四附属医院住院的患者61例,检测所有患者血三酰甘油、总胆固醇、低密度脂蛋白、血糖、单核细胞计数、超敏C反应蛋白、肌酐、β2微球蛋白水平;记录患者既往是否有高血压病、糖尿病、吸烟史.采用彩色多普勒超声仪观察颈动脉管壁内膜中层厚度.结果 两组间单因素比较显示斑块组年龄、高血压病发生率、糖代谢异常发生率、超敏C反应蛋白及吸烟水平高于非斑块组;两组间性别、总胆固醇、三酰甘油、低密度脂蛋白、单核细胞计数、肌酐、β2微球蛋白水平比较差异无统计学意义.Logistic回归分析结果显示年龄、收缩压及吸烟进入回归方程,并有统计学意义.结论 在本研究中发现年龄、收缩压及吸烟是颈动脉斑块形成的独立危险因素.%Objective To investigate the major factors of the formation of carotid atherosclerotic plaque so as to prevent cerebral arterial thrombosis. Methods A total of 61 inpatients admitted to Fourth Affiliated Hospital of Guangxi Medical University from December 2010 to March 2011 were included. They were measured the level of some possible risk fators including TG, TC, LDL, blood sugar, monocyte count, supersensitivity C reactive protein, creatinine, (32 microglobulin; the history of past illness including hypertensive disease, diabetes mellitus and smoking were recorded. The diacrisis of the formation of carotid atherosclerotic plaque was done according to the color Doppler to investigate layer thickness of endomembrane along the line feed of arteria carotis communis from lengthways and athwartships. Results The mean age, incidences of hypertension, abnormal glycome-tabolism, supersensitivity C reactive protein and smokings were higher in patients with carotid plaques than in

  20. Identification of periodontal pathogens in atherosclerotic vessels

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  1. Identification of periodontal pathogens in atherosclerotic vessels

    DEFF Research Database (Denmark)

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

    2005-01-01

    Epidemiological studies have shown that periodontitis may be associated with presence of atherosclerosis. DNA from periodontal pathogens has been detected in atherosclerotic lesions, but viable oral bacteria have not yet been isolated from atherosclerotic plaques. The purpose of the present study...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    cholesterol, inflammatory cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. RESULTS: High...... and a decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers. CONCLUSIONS: These data indicate that in a well-established model of obesity...

  3. 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

  4. Advances in the mechanisms of atherosclerosis vulnerable plague and endoplasmic reticulum stress

    Institute of Scientific and Technical Information of China (English)

    Zhong Zhang; Ruo-Lan Huang; Ru Mo; Ling Wang; Xiao Chang; Mu-Juan Xu

    2016-01-01

    Objective:Ischemic stroke and coronary heart disease occupy the first two place of world health economic burden, atherosclerotic vulnerable plaque rupture as the common factor of these diseases, is thought to be a key target of ischemic cardiovascular and cerebrovascular disease control. Endoplasmic reticulum stress is one of the classical pathway of cell apoptosis. More and more studies have indicated that the endoplasmic reticulum stress pathway was involved in the development of atherosclerotic plaque rupture. In this paper, the three main signal pathways of endoplasmic reticulum stress, including Protein kinase RNA-like ER kinase (PERK), Activating transcription factor 6 (ATF6) and Inositol-requiring protein 1αα(IRE1α) were reviewed. The relationship between the risk factors of atherosclerosis (including hyperlipidemia, hypertension and hyperglycemia) and endoplasmic reticulum stress, and the relationship between major cellular components (macrophages, vascular endothelial cells, vascular smooth muscle cells and vascular smooth muscle cells) of vulnerable plaque and endoplasmic reticulum stress were reviewed.

  5. Comparison of iodinated contrast media for the assessment of atherosclerotic plaque attenuation values by CT coronary angiography: Observations in an ex vivo model

    NARCIS (Netherlands)

    L. la Grutta (Ludovico); M. Galia (Massimo); G. Gentile; G. Lo Re (G.); E. Grassedonio (Emanuele); F. Coppolino; E. Maffei (Erica); E. Maresi (E.); A. Lo Casto (A.); F. Cademartiri (Filippo); M. Midiri (Massimo)

    2013-01-01

    textabstractObjective: To compare the influence of different iodinated contrast media with several dilutions on plaque attenuation in an ex vivo coronary model studied by multislice CT coronary angiography. Methods: In six ex vivo left anterior descending coronary arteries immersed in oil, CT (slice

  6. Site-specific nitration of apolipoprotein A-I at tyrosine 166 is both abundant within human atherosclerotic plaque and dysfunctional.

    Science.gov (United States)

    DiDonato, Joseph A; Aulak, Kulwant; Huang, Ying; Wagner, Matthew; Gerstenecker, Gary; Topbas, Celalettin; Gogonea, Valentin; DiDonato, Anthony J; Tang, W H Wilson; Mehl, Ryan A; Fox, Paul L; Plow, Edward F; Smith, Jonathan D; Fisher, Edward A; Hazen, Stanley L

    2014-04-11

    We reported previously that apolipoprotein A-I (apoA-I) is oxidatively modified in the artery wall at tyrosine 166 (Tyr(166)), serving as a preferred site for post-translational modification through nitration. Recent studies, however, question the extent and functional importance of apoA-I Tyr(166) nitration based upon studies of HDL-like particles recovered from atherosclerotic lesions. We developed a monoclonal antibody (mAb 4G11.2) that recognizes, in both free and HDL-bound forms, apoA-I harboring a 3-nitrotyrosine at position 166 apoA-I (NO2-Tyr(166)-apoA-I) to investigate the presence, distribution, and function of this modified apoA-I form in atherosclerotic and normal artery wall. We also developed recombinant apoA-I with site-specific 3-nitrotyrosine incorporation only at position 166 using an evolved orthogonal nitro-Tyr-aminoacyl-tRNA synthetase/tRNACUA pair for functional studies. Studies with mAb 4G11.2 showed that NO2-Tyr(166)-apoA-I was easily detected in atherosclerotic human coronary arteries and accounted for ∼ 8% of total apoA-I within the artery wall but was nearly undetectable (>100-fold less) in normal coronary arteries. Buoyant density ultracentrifugation analyses showed that NO2-Tyr(166)-apoA-I existed as a lipid-poor lipoprotein with nitration of apoA-I at Tyr(166) is an abundant modification within the artery wall that results in selective functional impairments. Plasma levels of this modified apoA-I form may provide insights into a pathophysiological process within the diseased artery wall.

  7. Optimization of K-edge imaging for vulnerable plaques using gold nanoparticles and energy resolved photon counting detectors: a simulation study.

    Science.gov (United States)

    Alivov, Yahya; Baturin, Pavlo; Le, Huy Q; Ducote, Justin; Molloi, Sabee

    2014-01-06

    We investigated the effect of different imaging parameters, such as dose, beam energy, energy resolution and the number of energy bins, on the image quality of K-edge spectral computed tomography (CT) of gold nanoparticles (GNP) accumulated in an atherosclerotic plaque. A maximum likelihood technique was employed to estimate the concentration of GNP, which served as a targeted intravenous contrast material intended to detect the degree of the plaque's inflammation. The simulation studies used a single-slice parallel beam CT geometry with an x-ray beam energy ranging between 50 and 140 kVp. The synthetic phantoms included small (3 cm in diameter) cylinder and chest (33 × 24 cm(2)) phantoms, where both phantoms contained tissue, calcium and gold. In the simulation studies, GNP quantification and background (calcium and tissue) suppression tasks were pursued. The x-ray detection sensor was represented by an energy resolved photon counting detector (e.g., CdZnTe) with adjustable energy bins. Both ideal and more realistic (12% full width at half maximum (FWHM) energy resolution) implementations of the photon counting detector were simulated. The simulations were performed for the CdZnTe detector with a pixel pitch of 0.5-1 mm, which corresponds to a performance without significant charge sharing and cross-talk effects. The Rose model was employed to estimate the minimum detectable concentration of GNPs. A figure of merit (FOM) was used to optimize the x-ray beam energy (kVp) to achieve the highest signal-to-noise ratio with respect to the patient dose. As a result, the successful identification of gold and background suppression was demonstrated. The highest FOM was observed at the 125 kVp x-ray beam energy. The minimum detectable GNP concentration was determined to be approximately 1.06 µmol mL(-1) (0.21 mg mL(-1)) for an ideal detector and about 2.5 µmol mL(-1) (0.49 mg mL(-1)) for a more realistic (12% FWHM) detector. The studies show the optimal

  8. Moderate Autophagy Inhibits Vascular Smooth Muscle Cell Senescence to Stabilize Progressed Atherosclerotic Plaque via the mTORC1/ULK1/ATG13 Signal Pathway

    Directory of Open Access Journals (Sweden)

    Zhenli Luo

    2017-01-01

    Full Text Available In order to investigate the effects of autophagy induced by rapamycin in the development of atherosclerosis plaque we established murine atherosclerosis model which was induced in ApoE−/− mice by high fat and cholesterol diet (HFD for 16 weeks. Rapamycin and 3-Methyladenine (MA were used as autophagy inducer and inhibitor respectively. The plaque areas in aortic artery were detected with HE and Oil Red O staining. Immunohistochemical staining were applied to investigate content of plaque respectively. In contrast to control and 3-MA groups, rapamycin could inhibit atherosclerosis progression. Rapamycin was able to increase collagen content and a-SMA distribution relatively, as well as decrease necrotic core area. Then we used MOVAS and culture with ox-LDL for 72 h to induce smooth muscle-derived foam cell model in vitro. Rapamycin and 3-MA were cultured together respectively. Flow cytometry assay and SA-β-Gal staining experiments were performed to detect survival and senescence of VSMCs. Western blot analysis were utilized to analyze the levels of protein expression. We found that rapamycin could promote ox-LDL-induced VSMCs autophagy survival and alleviate cellular senescence, in comparison to control and 3-MA groups. Western blot analysis showed that rapamycin could upregulate ULK1, ATG13 and downregulate mTORC1 and p53 protein expression.

  9. 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].

  10. High wall shear stress and high-risk plaque: an emerging concept.

    Science.gov (United States)

    Eshtehardi, Parham; Brown, Adam J; Bhargava, Ankit; Costopoulos, Charis; Hung, Olivia Y; Corban, Michel T; Hosseini, Hossein; Gogas, Bill D; Giddens, Don P; Samady, Habib

    2017-01-10

    In recent years, there has been a significant effort to identify high-risk plaques in vivo prior to acute events. While number of imaging modalities have been developed to identify morphologic characteristics of high-risk plaques, prospective natural-history observational studies suggest that vulnerability is not solely dependent on plaque morphology and likely involves additional contributing mechanisms. High wall shear stress (WSS) has recently been proposed as one possible causative factor, promoting the development of high-risk plaques. High WSS has been shown to induce specific changes in endothelial cell behavior, exacerbating inflammation and stimulating progression of the atherosclerotic lipid core. In line with experimental and autopsy studies, several human studies have shown associations between high WSS and known morphological features of high-risk plaques. However, despite increasing evidence, there is still no longitudinal data linking high WSS to clinical events. As the interplay between atherosclerotic plaque, artery, and WSS is highly dynamic, large natural history studies of atherosclerosis that include WSS measurements are now warranted. This review will summarize the available clinical evidence on high WSS as a possible etiological mechanism underlying high-risk plaque development.

  11. 磁共振成像用于区分冠状动脉斑块成分的Meta分析%Distinction of coronary atherosclerotic plaques with magnetic resonance imaging: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    王永智; 李云娟; 浦奎; 郭峰; 张会; 秘春敬

    2016-01-01

    Objective To review the feasibility and veracity of magnetic resonance imaging (MRI) in distinction of coronary atherosclerotic plaques by using Meta-analysis method.Methods The databases of Cochrane Library, PubMed, OVID, EBSCO, CNKI, CBM and WanFang Database were retrieved with computer until to Dec. 31, 2014 for collecting studies on distinction of coronary atherosclerotic plaques with MRI, and screening the documents according to the recommendation by Cochrane Collaboration. The documents were analyzed by using STATA 12.0 software and Meta-disc 1.4 software, including heterogeneity test, public bias test, Meta-regression, clinical pragmatic investigation, pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR) and 95% confidence interval (95%CI). The summary receiver operating characteristic curve (SROC) and area under curve (AUC) were drawn and calculated. Results There were totally 6 documents included. SEN was [0.92 (95%CI: 0.86~0.9), SPE was [0.89 (95%CI:0.82~0.94)], DOR was [56.09 (95%CI: 18.41~212.49)], and AUC was 0.9451 in summarized identification of lipid-rich composition. SEN was [0.88 (0.79~0.94)], SPE was [0.96 (0.91~0.98)], DOR was [78.95 (22.01~283.28)], and AUC was 0.9291 in identification of calcification composition.Conclusion MRI is highly accurate in distinction of lipid-rich composition and calcification composition in coronary atherosclerotic plaques.%目的 用Meta分析的方法评价磁共振成像区分冠状动脉粥样斑块组成成分的可行性及准确性.方法 计算机检索Cochrane Library、PubMed、OVID、EBSCO、中国期刊全文数据库、中国生物医学文献数据库和万方数据库,时间截止至2014年12月31日.纳入关于磁共振成像识别区分冠状动脉粥样硬化斑块成分的研究文献,结合Cochrane协作网推荐内容制定纳入标准筛选文献,然后采用STATA 12.0和Meta-disc 1.4软件对资料进行统计分析,包括异质性检验、发表偏倚检测、Meta回归

  12. 冠状动脉血管内超声优化临界病变易损斑块诊治的研究%Coronary intravascular ultrasonography optimizes diagnosis and treatment of vulnerable plaque in intermediate stenosis

    Institute of Scientific and Technical Information of China (English)

    冯瑞; 雷家俨; 黄玮

    2013-01-01

    目的 通过对比冠状动脉(简称冠脉)临界病变患者定量冠脉造影(quantitative coronary angiography,QCA)与血管内超声(intravascular ultrasound,IVUS)的测量结果,评价IVUS能否优化冠脉临界病变的诊断和治疗.方法 通过QCA和IVUS对19名冠脉临界病变患者粥样硬化斑块处的最小管腔直径(minimal lumen diameter,MLD)、面积狭窄率(area stenosis,%AS)及直径狭窄率(diameter stenosis,%DS)等参数进行分析.应用IVUS及血管内超声-虚拟组织学(iMAP-IVUS)分析软件观察斑块类型、性质及组成成分,并对IVUS提示狭窄程度≥70%的冠脉病变行支架植入术.结果 QCA与IVUS显示的MLD、%DS及%AS值分别为(1.75 ±0.39)mm vs(2.07±0.40) mm;(35.04±13.60)%vs(46.37±8.02)%;(52.91±15.96)% vs (62.61 ±11.54)%,两者比较差异均有统计学意义(P<0.05).QCA检出合并心肌桥患者7例(36.8%),IVUS检出10例(52.6%).采用IVUS对19例病变进行分析,其中软斑63.2%,硬斑15.8%,钙化斑块10.5%,混合斑块10.5%;偏心性斑块84.2%,向心性斑块15.8%;正性重构57.9%,无重构15.8%,负性重构26.3%.采用iMAP-IVUS对19例病变的成分进行测定,共发现TCFA14例.初步预测正性重构可能与斑块不稳定性有关.结论 IVUS可提高冠脉临界病变诊断的准确率,发现易损斑块,对高危患者进行及早干预治疗,且安全性高.%Objective To determine the value of intravascular ultrasound (IVUS ) in optimization of diagnosis and treatment in coronary intermediate stenosis, by comparing its results with those by quantitative coronary angiography (QCA).Methods Clinical data of 19 patients who received QCA and identified with stenosis between 40% to 70% in our department from October 2010 to December 2011 were enrolled in this study.QCA and IVUS was used to analyze the parameters of atherosclerotic plaques in the patients with intermediate stenosis, such as, minimal lumen diameter ( MLD) , area

  13. 大脑中动脉粥样硬化斑块与单发性皮质下梗死的相关性%Correlation between middle cerebral artery atherosclerotic plaques and single subcortical infarction

    Institute of Scientific and Technical Information of China (English)

    王可颜; 程敬亮; 张勇

    2015-01-01

    Objective To investigate the correlation between middle cerebral artery (MCA) atherosclerotic plaques and single subcortical infarction (SSI) using high-resolution magnetic resonance imaging (HR-MRI).Methods The patients with SSI received HR-MRI examinations at the ipsilateral MCA horizontal segment stenosis from January 2012 to November 2014 were analyzed prospectively.They were divided into proximal SSI (pSSI) and distal SSI (dSSI).The longitudinal and transverse diameters and volume of different types of infarction pattern as well as the degree of luminal stenosis of MCA deep perforating parent artery,plaque distribution,plaque enhancement or not,white matter lesions,and general information of both groups were documented respectively.Results A total of 78 patients with SSI were enrolled,including 40 (51%) in the pSSI group and 38 (49%) in the dSSI group.The proportions of Fazekas scale grade 3 white matter lesions (63.5%vs.40.0%;x2 =4.183,P=0.041) and deep white matter lesions (50.0% vs.15.0%;x2 =10.961,P =0.001) in the dSSI group were significantly higher than those in the pSSI group.The proportions of MCA plaque in the opening (35.0% vs.13.2%;x2=3.930,P=0.047),plaque enhancement (87.5% vs.30.0%;x2 =25.447,P < 0.001) and posterosuperior wall plaques (42.5% vs.21.4%;x2 =9.491,P < 0.001) and the degree of luminal stenosis (60.38% ± 10.20% vs.45.00% ±6.44%;t =3.625,P =0.031) in the pSSI group were all significantly higher than those in the dSSI group.In addition,the longitudinal and transverse diameters and volume of the infarcts in the pSSI group were significantly larger than those in the dSSI group (all P < 0.001).Multivariate logistic regression analysis showed that MCA enhanced plaques on the lesionipsilateral sides (odds ratio[OR] 11.764,95% confidence interval[CI] 2.081-66.511;P =0.005) and posterosuperior wall plaques (OR 6.131,95% CI 1.012-23.339;P =0.037) were independently associated with pSSI,while deep white

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

    Directory of Open Access Journals (Sweden)

    Jamal Shamsara

    2009-05-01

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

  15. The effects of the mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease. A randomized trial.

    Directory of Open Access Journals (Sweden)

    Rosa Casas

    Full Text Available BACKGROUND: Adherence to the Mediterranean diet (MD is associated with reduced morbidity and mortality due to cardiovascular disease. However, how the MD exerts its effects is not fully known. AIM: To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED (Prevención con Dieta Mediterránea study. METHODS: A total of 164 participants at high risk for cardiovascular disease were randomized into three diet groups: MD supplemented with 50mL/d of extra virgin olive oil (MD+EVOO or 30 g/d of nuts (MD+Nuts and a low-fat diet. Changes in classical cardiovascular risk factors, inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention. RESULTS: Compared to participants in the low-fat diet group, those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic (6mmHg and diastolic (3mmHg blood pressure (P = 0.02; both, as well as a reduction of 10% and 8% in LDL-cholesterol (P = 0.04, respectively. Patients in the MD+Nuts group showed a significant reduction of 34% in CD40 expression on monocyte surface compared to low-fat diet patients (P = 0.03. In addition, inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45% and 35% and 95% and 90% in the MD+EVOO and MD+Nuts groups, respectively (P<0.05; all compared to the low-fat diet group. Likewise, sICAM and P-selectin were also reduced by 50% and 27%, respectively in the MD+EVOO group (P = 0.04 and P-selectin by 19% in MD+Nuts group (P = 0.04 compared to the low-fat diet group. CONCLUSIONS: Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain, at least in part, the protective role of MD against ischemic heart disease. TRIAL REGISTRATION: www.controlled-trials.com ISRCTN

  16. Meta-analysis of Clinical Efficacy of Chinese Medic ine on Carotid Atherosclerotic Plaque%中医药治疗颈动脉粥样硬化斑块临床疗效的 Meta分析

    Institute of Scientific and Technical Information of China (English)

    刘梨; 龚后武; 张建影; 常小荣

    2015-01-01

    目的:系统评价中医药相关疗法对颈动脉粥样硬化斑块的临床疗效。方法:计算机检索The Co-chrane Library、PubMed、CBM、CNKI、WanFang Data及VIP,收集有关中医药治疗颈动脉粥样硬化斑块的随机对照试验( RCT),检索时限从建库至2014年8月,由两位研究者根据纳入及排除标准独立筛选文献、提取信息及评价纳入文献的方法学质量后,采用软件Rev Man 5.2.9进行Meta分析。结果:最终纳入10个RCT,共计1006例患者,干预措施治疗组为中医药相关疗法,对照组均为常规西药治疗。 Meta分析结果显示:与常规西药用药相比,中医药干预组能显著改善临床证候[OR=2.08,95%CI(1.50,9.55),P=0.004];颈动脉内中膜厚度影响方面,中医药较单纯西药治疗有效,其差异有统计学意义[MD=-0.06,95%CI(-0.10,-0.03),P=0.0006];对降低硬化斑块体积/面积,中医药干预组也较对照组明显( P<0.00001)。结论:在治疗颈动脉粥样硬化斑块方面,中医药干预组的疗效优于常规西药用药组。因纳入研究质量较低,数量所限,故上述结论仍需开展更多大样本高质量的RCT加以验证。%Objective:To evaluate the clinical efficacy of TCM therapy on the carotid atherosclerotic plaque.Methods:Search The Cochrane Library, PubMed, CBM, CNKI, WanFang Data and VIP and collect information of randomized controlled trial ( RCT) about Chinese medicine treatment for carotid atherosclerotic plaque, building a database to re-trieve the time to August 2014 .Two reviewers independently screened the literatures based on inclusion and exclusion criteria,and extracted information and evaluation methods including studies after methodology quality by use of software RevMan 5.2.9 Meta-analysis.Results:Including 10 RCT, totally 1006 cases of patients, the treatment group was trea-ted with interventions of Chinese

  17. Effective of Vitamin E Combined with Vitamin C for the Intervention of Carotid Atherosclerotic Plaques%维生素E联合维生素C对颈动脉粥样斑块的干预作用研究

    Institute of Scientific and Technical Information of China (English)

    王玉红; 王玉起; 李万福; 张雪芹

    2013-01-01

    目的 探讨维生素E联合维生素C对颈动脉粥样斑块的干预作用,为防治动脉粥样硬化提供依据.方法 选择大兴黄村镇5个社区45岁以上经颈动脉超声检查明确有颈动脉硬化斑块及颈动脉内膜中层厚度(IMT)≥1.0 mm的患者196例为研究对象,在常规应用阿司匹林肠溶片及他汀类降脂药治疗的基础上按随机数字表法随机分为A组(加服维生素E 200 mg/晚)、B组(加服维生素E 200 mg/晚,维生素C 200 mg 早晚各1次)、C组(加服维生素C 200 mg 早晚各1次)及对照组(不加服维生素E和C).干预18个月后,对干预前后斑块大小变化进行分析.结果 干预前、后4组患者颈动脉粥样斑块组间比较,差异均无统计学意义(P>0.05).组内比较,对照组干预前后颈动脉粥样斑块间差异有统计学意义(P<0.05),A组、B组、C组干预前后斑块间差异均无统计学意义(P>0.05).结论加用维生素E和(或)维生素C对颈动脉粥样斑块没有明显缩小的作用.%Objective To explore the effectiveness of vitamin E combined with vitamin C in the intervention of carotid atherosclerotic plaques ( CAPs ). Methods A total of 196 45 - year - old - or - above patients with ultrasound - confirm CAPs ( and carotid intima media thickness≥ 1. 0 mm ) from 5 communities in Huangcun, Daxing District, Beijing, were enrolled. In addtion to routine aspirin and statin therapy, patients were further divided into four groups based on the administration of vitamins : group A ( supplemented with vitamin E, 200 mg/day ), group B ( supplenmented with vitamin E 200 mg, qn, and vitamin C 200 mg bid ), group C ( supplemented with vitamin C 200 mg bid ), and control group ( without any vitamin supplementation). After 18 months of treatment, the change in the size of CAPs were compared among these four groups. Results Compared with the control group, the size of CAPs in groups A, B, and C were not significantly different ( P >0. 05 ). The control

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-02-15

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

  19. 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...

  20. Endothelial microparticles as conveyors of information in atherosclerotic disease.

    Science.gov (United States)

    Schiro, A; Wilkinson, F L; Weston, R; Smyth, J V; Serracino-Inglott, F; Alexander, M Y

    2014-06-01

    Endothelial microparticles (EMPs) are complex submicron membrane-shed vesicles released into the circulation following endothelium cell activation or apoptosis. They are classified as either physiological or pathological, with anticoagulant or pro-inflammatory effects respectively. Endothelial dysfunction caused by inflammation is a key initiating event in atherosclerotic plaque formation. Athero-emboli, resulting from ruptured carotid plaques are a major cause of stroke. Current clinical techniques for arterial assessment, angiography and carotid ultrasound, give accurate information about stenosis but limited evidence on plaque composition, inflammation or vulnerability; as a result, patients with asymptomatic, or fragile carotid lesions, may not be identified and treated effectively. There is a need to discover novel biomarkers and develop more efficient diagnostic approaches in order to stratify patients at most risk of stroke, who would benefit from interventional surgery. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. In this review, we will present the evidence to support this hypothesis and propose a novel concept for the development of a diagnostic device that could be implemented in the clinic. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Oxidized LDL in carotid plaques and plasma associates with plaque instability

    National Research Council Canada - National Science Library

    Nishi, Kyoko; Itabe, Hiroyuki; Uno, Masaaki; Kitazato, Keiko T; Horiguchi, Hidehisa; Shinno, Kiyohito; Nagahiro, Shinji

    2002-01-01

    Oxidation of LDL plays a significant pathogenic role in atherosclerosis. In this study, we attempted to clarify the correlation between the morphology of human atherosclerotic plaques and the oxidized LDL (OxLDL...

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

    Institute of Scientific and Technical Information of China (English)

    Guo-ShengYang; Zhao-DianChen; Hong-JuWang

    2004-01-01

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

  3. Carotid ultrasound phenotypes in vulnerable populations

    Directory of Open Access Journals (Sweden)

    Spence J David

    2006-11-01

    Full Text Available Abstract Background Biomarkers of carotid atherosclerosis range from those that are widely available and relatively simple to measure such as serum cholesterol levels, and B-mode Ultrasound measurement of intima media thickness (IMT to those that are more complex and technologically demanding but perhaps potentially more sensitive and specific to disease such as total plaque volume and total plaque area measured from 3-dimensional ultrasound images. In this study we measured and compared intima media thickness (IMT, total plaque volume (TPV and total plaque area (TPA in two separate populations, both vulnerable to carotid atherosclerosis. Methods In total, 88 subjects (mean age 72.8 with carotid stenosis of at least 60%, based on a peak Doppler flow, and 82 subjects (mean age 60.9 with diabetic nephropathy were assessed in a cross-sectional study. Conventional atherosclerotic risk factors were examined and the associations and correlations between these and carotid ultrasound phenotypes measured from B-mode and 3-dimensional ultrasound images were assessed. Results IMT and TPV were only modestly correlated in the two separate populations (r = .6, p Conclusion IMT and TPV were modestly correlated in a diabetic patient population and only TPV was associated with diabetes and the presence of plaque ulcerations in a diabetic population and carotid stenosis group. The 3-dimensional information provided by TPV can be critically important in unmasking association with risk factors not observed with less complex single-dimension assessments of carotid atherosclerosis such as those provided by IMT.

  4. Observation of curative effects of trigeminy therapy with probucol, antiplatelet agents and statins on atherosclerotic plaque of the carotid in cerebral infarction patients%抗氧化、抗血小板和降脂三联疗法治疗脑梗死患者颈动脉粥样硬化斑块的疗效观察

    Institute of Scientific and Technical Information of China (English)

    李绍发; 梁柯

    2011-01-01

    Objective To observe the curative effects of trigeminy therapy with probucol, antiplatelet agents and statins (PAS) on atherosclerotic plaque of the carotid in cerebral infarction patients. Methods One hundred and eighty cerebral infarction patients with atherosclerotic plaque of the carotid were randomly devided into PAS trigeminy therapy group (PAS group, 60 cases), atorvastatin therapy group (atorvastatin group, 60 cases) and aspirin therapy group (control group, 60 cases). The blood total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), iow density lipoprotein ( LDL), oxidized LDL (ox-LDL) and high sensitive C reactive protein (hs-CRP) of all the patients were determined before and after treatment. The carotid intima and media thickness (IMT) and the area of atherosclerotic plaque of the carotid were detected by color Doppler ultrasound. Results Compared with before treatment, the serum levels of TC, TG, LDL, ox-LDL and hs-CRP of patients in atorvastatin group were significantly decreased after treatment ( all P <0. 01 ); the IMT and the area of atherosclerotic plaque of the carotid were significantly decreased ( all P < 0. 05 ). After treatment, compared with atovastatin group, the serum levels of TC, TG, LDL, ox-LDL and hs-CRP in PAS group were significantly decreased ( P < 0.05 - 0. 01 ); the IMT and the area of atherosclerotic plaque of the carotid in PAS group were significantly decreased ( all P < O.05 ).Conclusion The PAS trigeminy therapy has notable curative effects on atheroscleretic plaque of the carotid in cerebral infarction patients, and there is no obvious adverse reaction.%目的:观察抗氧化、抗血小板和降脂(PAS)三联疗法治疗脑梗死患者颈动脉粥样硬化斑块的疗效.方法:180例确诊颈动脉粥样硬化斑块的脑梗死患者随机分成PAS三联疗法治疗组(PAS组,60例)、阿托伐他汀钙治疗组(他汀组,60例)和拜阿司匹林治疗组(对照组,60例).检测各患者治疗

  5. 高分辨磁共振成像对颈动脉粥样硬化斑块表面钙化与斑块稳定性关系研究%Correlated study on superficial calcification and stability of carotid atherosclerotic plaque using high resolution MRI

    Institute of Scientific and Technical Information of China (English)

    彭少华; 王成伟; 尹喜

    2012-01-01

    Objective To evaluate the relationship of the shape,location of superficial calcification with stability of carotid atherosclerotic plaque using high resolution magnetic resonance imaging(MRI). Methods High resolution MRI was performed in the carotid artery of 34 patients with four sequences.including 3D-TOF,DIR T1WI,FSE T2WI and PDWI. The shape, location of superficial calcification with surface ulcer of carotid atherosclerotic plaque were evaluated. Results Out of 87 slices of superficial calcification, 59 slices plaques (67. 8%) showed surface ulcer. According to calcification type and location,64 slices were irregular (dotted/arcuated) calcification type,23 slices patch type,58 slices marginal calcification type and 29 slices central calcification type. Irregular superficial calcification was found more frequently with surface ulcer than patch calcification type. Marginal calcification type had higher possibility of surface ulcer than central calcification type. Conclusion Superficial calcification is an important factor for instability of atherosclerotic carotid plaque,which easily brings about surface ulcer on the carotid atherosclerotic plaque. The shape and location of superficial calcification are important factors of instability for atherosclerotic carotid plaque.%目的 通过高分辨磁共振成像(MRI)多序列扫描,分析颈动脉粥样硬化斑块的表面钙化的形状、位置与斑块稳定性的关系.方法 运用高分辨MRI多序列(3D-TOF、DIR T1WI、FSE T2WI、PDWI)对34例颈动脉斑块患者进行扫描,分析钙化类型和位置与斑块表面溃疡的关系.结果 87层表面钙化斑块,59层(67.8%)见斑块表面溃疡.按钙化类型和部位划分,64层为点状、弧形的不规则钙化,23层为大片状钙化;58层为边缘钙化,29层为中央钙化.不规则钙化组伴斑块表面溃疡的概率显著高于大片状钙化组;边缘钙化组较中央钙化组更易伴斑块表面溃疡.结论 表面钙化是斑块不稳

  6. 急性心肌梗死患者颈动脉粥样硬化斑块易损性与血脂、血压相关性研究%Patients with acute myocardial infarction death carotid atherosclerotic plaques and blood fat and blood pressure correlation.

    Institute of Scientific and Technical Information of China (English)

    张海英; 王玉霞; 陈方焘(通讯作者)

    2012-01-01

      目的:探讨急性心肌梗死患者血脂浓度、血压与颈动脉(IMT)粥样硬化斑块的关系.方法:应用彩色多普勒超声检查急性心肌梗死患者的颈动脉内膜—中膜厚度,斑块数和性状,同时检测血压、血脂.186例急性心肌梗死患者根据有无高血压,分为心肌梗死组 A 组47例、高血压并发心肌梗死组 B 组139例,设健康体验者作对照组 C 组70例.各种数据进行统计学分析.结果:B 组颈动脉粥样硬化斑块发生率最高(94.8%),且以软斑及混合斑为主,A 组次之(66.1%),C 组最低(22.9%).与无颈动脉粥样硬化斑块相比,有颈动脉粥样硬化斑块患者血清低密度脂蛋白胆固醇(LDL-C)水平明显升高.结论:颈动脉粥样硬化斑块是急性心肌梗死的重要危险因素,高血压及高 LDL-C 血症是颈动脉粥样硬化的危险因素.%  Objective in patients with acute myocardial infarction blood lipid concentration, blood pressure and carotid artery (IMT) atherosclerotic plaque relationship. Methods Color doppler ultrasound of acute myocardial infarction with carotid endarterectomy, film thickness, plaques number and characters, and measure blood pressure, cholesterol. 186 cases of acute myocardial infarction patients have according to high blood pressure, divided into A group of myocardial infarction 47 cases were, pressure and myocardial infarction group B group 139 examples, set the experience for the control group C health group 70 examples. The statistical analysis of the data. Result The group B carotid atherosclerotic plaques was highest (94.8%), and with the soft spot and mixed spot is given priority to, A second group (66.1%), the lowest group C (22.9%). And no carotid atherosclerotic plaques in carotid atherosclerotic plaques patients serum low density lipoprotein cholesterol (LDL)-C) a significantly higher level. Conclusion Carotid atherosclerotic plaque with acute myocardial infarction is an important risk factors

  7. Atherosclerotic plaque burdens in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ In this issue of the Journal of Geriatric Cardiology,Huang et al. have reported the detection of coronary artery disease with electron-beam computed tomography (EBCT),utilizing non-contrast and contrast imaging techniques (EBCTA) in several subgroups including type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT), coronary heart disease, and normal subjects.

  8. PI3K/Akt/mTOR信号通路在巨噬细胞自噬及动脉粥样硬化斑块不稳定中的作用%Roles of PI3K/Akt/mTOR signaling pathway in macrophage autophagy and atherosclerotic plaque instability

    Institute of Scientific and Technical Information of China (English)

    王和峰; 翟纯刚; 庞文会; 王晨; 杨敏; 赵凯; 李大庆; 张运; 李继福

    2013-01-01

    whether selective inhibition of the phosphatidylinositol 3-kinase (PI3K)/pro-tein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway stabilizes the vulnerable atherosclerotic plaques by promoting macrophage autophagy. METHODS; In in vitro study, casodex (20 μmol/L) , rapamycin (10 nmol/L) or mTOR-siRNA (30 nmol/L) was used to treat mouse macrophage cell line RAW 264. 7. Inflammation-related cytokines secreted by macrophages were measured by means of ELJSA. Ultrastructural changes of the macrophages were examined by transmission electron microscopy. The mRNA and protein expression levels of Akt, mTOR and autophage-related protein Beclin 1 were assayed by real-time fluorescence quantitative RT-PCR and Western blotting. The expression of autophagy-related indicator LC3-II was detected by immunofluorescence and Western blotting. In in vivo study, 24 New Zealand white rabbits underwent balloon-induced abdominal aortic wall injury and were fed with a diet of 1% cholesterol for 8 weeks. The rabbits were randomly divided into control group (n=8), casodex group (1.0 mg·kg-1·d-1, n = 8) and rapamycin group (0. 5 mg· kg-1·d-1 , n=8). Four weeks after drug administration, intravascular ultrasound (IVUS) was carried out to observe the plaque imaging. Ultrastructural changes of the macrophages and the protein expression of Akt, mTOR and LC3-II in the macrophages were also measured. RESULTS; In in vitro study, more typical autophago-somes were detected in casodex-, rapamycin- or mTOR-siRNA-treated cells. The expression level of LC3-II increased, but Beclin 1 ,p-Akt and p-mTOR significantly decreased in the 3 treatment groups. The concentration of IL-10 decreased while IFN-γ significantly increased in the treatment groups. In in vivo study, IVUS found that external elastic membrane area (EEMA) ,plaque area(PA) and plaque burden (PB) significantly decreased in casodex and rapamycin treatment groups. Expression of LC3-II increased significantly in the 2 treatment

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

    Institute of Scientific and Technical Information of China (English)

    王小飞; 陈欣; 王佩显

    2011-01-01

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

  10. Identification of High-Risk Plaques by MRI and Fluorescence Imaging in a Rabbit Model of Atherothrombosis.

    Directory of Open Access Journals (Sweden)

    Ning Hua

    Full Text Available The detection of atherosclerotic plaques at risk for disruption will be greatly enhanced by molecular probes that target vessel wall biomarkers. Here, we test if fluorescently-labeled Activatable Cell Penetrating Peptides (ACPPs could differentiate stable plaques from vulnerable plaques that disrupt, forming a luminal thrombus. Additionally, we test the efficacy of a combined ACPP and MRI technique for identifying plaques at high risk of rupture.In an atherothrombotic rabbit model, disrupted plaques were identified with in vivo MRI and co-registered in the same rabbit aorta with the in vivo uptake of ACPPs, cleaved by matrix metalloproteinases (MMPs or thrombin. ACPP uptake, mapped ex vivo in whole aortas, was higher in disrupted compared to non-disrupted plaques. Specifically, disrupted plaques demonstrated a 4.5~5.0 fold increase in fluorescence enhancement, while non-disrupted plaques showed only a 2.2~2.5 fold signal increase. Receiver operating characteristic (ROC analysis indicates that both ACPPs (MMP and thrombin show high specificity (84.2% and 83.2% and sensitivity (80.0% and 85.7% in detecting disrupted plaques. The detection power of ACPPs was improved when combined with the MRI derived measure, outward remodeling ratio.Our targeted fluorescence ACPP probes distinguished disrupted plaques from stable plaques with high sensitivity and specificity. The combination of anatomic, MRI-derived predictors for disruption and ACPP uptake can further improve the power for identification of high-risk plaques and suggests future development of ACPPs with molecular MRI as a readout.

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

    Institute of Scientific and Technical Information of China (English)

    陈近利; 陈吉棣

    2001-01-01

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

  12. Carotid Magnetic Resonance Imaging A Window to Study Atherosclerosis and Identify High-Risk Plaques

    National Research Council Canada - National Science Library

    Oikawa, Minako; Ota, Hideki; Takaya, Norihide; Miller, Zach; Hatsukami, Thomas S; Yuan, Chun

    2009-01-01

    ...: the so-called "vulnerable plaque". A reliable, in vivo, imaging method capable of identifying plaque characteristics associated with high-risk plaque will be immensely useful for evaluating plaque status and predicting future events...

  13. To evaluate the composition and typing of carotid artery atherosclerotic plaque and the relationship between plaque morphology and clinical symptoms%MRI评估颈动脉粥样硬化斑块成分、类型及其与临床症状的相关性

    Institute of Scientific and Technical Information of China (English)

    罗南; 刘一; 范占明

    2013-01-01

    Objective To compare plaque morphology from patients with and without stroke symptoms, determine the relationship between carotid plaque morphology and stroke pathogenesis, and evaluate the warning function of high-field MR on early diagnosis of plaque. Methods Patients with carotid artery atherosclerotic plaque detected by B-mode ultrasonography were examined with MR imaging. Imaging was performed with a 3.0-T MR imager (Philips or GE) and a special 8-channel phased-array surface coil for carotid artery. The protocols include T1-, intermediate-, T2-, and post-contrast T1-weighted MR imaging, as well as three-dimensional time-of-flight (TOF) and MP-RAGE. All examinations were performed with a 14cm field of view, a matrix of 256 × 256 pixels,a 2-mm section thickness, and two acquired signals. An intersection space of -1 mm was used for three-dimensional TOF angiography and MP-RAGE, whereas no intersection space was used for MR imaging. Gadopentetate Dimeglumine was the contrast agent with the dosage of 0.1 mmol/Kg(0.2 ml/Kg)and injection speed of 0.7 ml/s. One observer recorded quantitative and morphologic information, which included measurement of the area of the lumen and main plaque components (calcification, hemorrhage, loose matrix ); fibrous cap status (thick, thin, or ruptured); reformed MR lesion type (types Ⅰ-Ⅷ) based on American Heart Association (AHA). Plaques associated with neurologic symptoms(transient ischemic attack, amaurosis fugax, or stroke appropriate to the distribution of the index carotid artery)and asymptomatic plaques were compared with Independent-sample T test on luminal stenosis, chi square test on occurrence rate of main plaque components and fibrous cap rupture respectively and regression analysis for the connection strength between plaque components and clinical symptoms. Results 64 carotid artery enrolled in the symptomatic group and 131 carotid artery enrolled in the asymptomatic group. Compared with asymptomatic plaques

  14. 格列吡嗪合并辛伐他汀对颈动脉粥样硬化斑块的疗效观察%Therapeutic Efficacy of Simvastatin plus Glipizide in Patients with Carotid Atherosclerotic Plaques

    Institute of Scientific and Technical Information of China (English)

    胡军; 曾慰; 胡名松

    2011-01-01

    目的:研究辛伐他汀对治疗并发高脂血症的颈动脉粥样硬化斑块的影响,以及合用格列吡嗪对辛伐他汀的增效作用.方法:将高脂血症并发颈动脉粥样硬化患者108例,随机分为2组,辛伐他汀治疗组和格列吡嗪合并辛伐他汀治疗组,6个月治疗后,测量血脂生化指标、炎症因子活性和高频率彩色多普勒超声内-中膜厚度(IMT).结果:两个治疗组,治疗后与治疗前相比,血脂指标,炎症因子指标及其IMT值都具有显著性差异(P0.05),但LDL-C显著减少(P<0.05),两组间ET-1和TNF-α以及IMT值差异显著(P<0.05).结论:辛伐他汀能够改善血脂水平,降低炎症因子活性,进而对颈动脉粥硬化具有治疗作用,而合并格列吡嗪治疗能够起到增效作用.%Objective: To evaluate the therapeutic efficacy of simvastafin in patients with carotid atherosclerotic plaques complicated with hyperlipidemia,and the synergistic effect of glipizide. Methods: All the 108 patients were divided into two groups group treatment with simvastatin and group treatment with simvastatin and glipizide. After treatment for 6 months, we measured the biochemical indicator of blood fat, included TC,TG,LDL-C and HDL-C ,the activity of inflammatory factors, included ET-1 and TNF-α, and the intima-media thickness (IMT). Results: Both of the 2 groups, the scores of biochemical indicator of blood lipids, activity of inflammatory factors and intima-media thickness (IMT) were changed significantly after treatment (P<0.05). Compared with group treatment with simvastatin, the changes of the scores of TC, TG and HDL-C were not significant (P>0.05). However, the scores of LDL-C, activity of inflammatory factors and IMT were decreased significantly (tP<0.05). Conclusiom: Simvastatin could improve carotid atherosclerosis, through improving the level of blood iipids and reducing the activity of inflammatory factors, and glipizide had a synergistic effect.

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

    Directory of Open Access Journals (Sweden)

    Natalia R. Lausada

    2007-10-01

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

  16. Molecular MRI of Atherosclerotic lesions

    NARCIS (Netherlands)

    Adel, Brigit den

    2013-01-01

    This thesis describes the use of MRI contrast agents and vessel wall parameters to image different stages of atherosclerosis. Chapter 2 summerizes different MRI contrast agents targeted towards vulnerable plaques that have been presented in literature. Chapter 3 illustrates accumulation of paramagn

  17. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

    Directory of Open Access Journals (Sweden)

    N. V. Pizova

    2014-01-01

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

  18. Towards coronary plaque imaging using simultaneous PET-MR: a simulation study

    Science.gov (United States)

    Petibon, Y.; El Fakhri, G.; Nezafat, R.; Johnson, N.; Brady, T.; Ouyang, J.

    2014-03-01

    Coronary atherosclerotic plaque rupture is the main cause of myocardial infarction and the leading killer in the US. Inflammation is a known bio-marker of plaque vulnerability and can be assessed non-invasively using fluorodeoxyglucose-positron emission tomography imaging (FDG-PET). However, cardiac and respiratory motion of the heart makes PET detection of coronary plaque very challenging. Fat surrounding coronary arteries allows the use of MRI to track plaque motion during simultaneous PET-MR examination. In this study, we proposed and assessed the performance of a fat-MR based coronary motion correction technique for improved FDG-PET coronary plaque imaging in simultaneous PET-MR. The proposed methods were evaluated in a realistic four-dimensional PET-MR simulation study obtained by combining patient water-fat separated MRI and XCAT anthropomorphic phantom. Five small lesions were digitally inserted inside the patients coronary vessels to mimic coronary atherosclerotic plaques. The heart of the XCAT phantom was digitally replaced with the patient's heart. Motion-dependent activity distributions, attenuation maps, and fat-MR volumes of the heart, were generated using the XCAT cardiac and respiratory motion fields. A full Monte Carlo simulation using Siemens mMR's geometry was performed for each motion phase. Cardiac/respiratory motion fields were estimated using non-rigid registration of the transformed fat-MR volumes and incorporated directly into the system matrix of PET reconstruction along with motion-dependent attenuation maps. The proposed motion correction method was compared to conventional PET reconstruction techniques such as no motion correction, cardiac gating, and dual cardiac-respiratory gating. Compared to uncorrected reconstructions, fat-MR based motion compensation yielded an average improvement of plaque-to-background contrast of 29.6%, 43.7%, 57.2%, and 70.6% for true plaque-to-blood ratios of 10, 15, 20 and 25:1, respectively. Channelized

  19. 孤立性颈动脉粥样硬化斑块内膜长轴切面力学状态的初步超声研究%Preliminary longitudinal mechanical pattern study of the isolated carotid atherosclerotic plaque intima using velocity vector imaging

    Institute of Scientific and Technical Information of China (English)

    岳文胜; 尹立雪; 王珊; 邓燕; 左明良; 李爽; 余洋; 罗安果

    2008-01-01

    Objective To evaluate the mechanical homogeneity pattern of isolated carotid atherosclerotic plaque intima on longitudinal axis view using ultrasonic velocity vector imaging.Methods Fourty six patients with 48 isolated plaques were undergone the high frequency ultrasound scanning,the real-time two-dimensional longitudinal-axis gray scale view at the maximal thickness of the plaque was obtained in three complete cardiac cycles.A dedicated velocity vector imaging(ⅤⅤⅠ)workstation was used for the off-line dynamic two-dimensional gray-scale image analysis and mechanics parameter(i.e.,the peak strain and the absolute difference of the peak strain)assessment at the sites of the upper,middle and down stream separately.The length and direction distribution of the velocity vectors at the carotid atherosclerotic plaque intima were observed.Wilcoxon test was utilized for the comparison of the peak strain and the absolute difference of the peak strain between two sites.Results The chaos phenomenon of velocity vector distribution at the sites of plaque intima occurred significantly differed from those uniform velocity vectors at the reference sites.According to the two groups of the higher strain value side and the lower strain value side on the upper stream and the down stream of the plaque intima,the peak strain at the higher strain value side was significantly higher than the lower strain value side(P=0.000).There was a significantly difference between the absolute difference of peak strain from the higher strain value side to the middle stream point of the plaque intima and the absolute difference of peak strain from the lower strain value side to the higher strain value side of the plaque intima(P<0.017).Conclusions The length and direction distribution of velocity vectors of the isolated carotid atherosclerotic plaque intima on longitudinal axis view are uneven,the mechanical heterogeneity pattern exists at the plaque intima and could be visualized and

  20. Comparison of blood leukocyte telomere DNA content and vascular telomere DNA content in human carotid atherosclerotic plaques%人颈动脉粥样硬化斑块组织及外周血白细胞相对端粒长度的检测及相关性分析

    Institute of Scientific and Technical Information of China (English)

    陈宇; 刘继斌; 刘鹏; 叶志东; 张伟丽; 惠汝太

    2012-01-01

    目的 研究人颈动脉粥样硬化斑块组织与外周血白细胞的DNA相对端粒长度是否有相关性,外周血白细胞能否反映血管组织的相对端粒长度,从而为外周血白细胞端粒长度与动脉粥样硬化的相关性研究提供依据.方法 分别取12例颈动脉内膜剥脱术患者的颈动脉内膜斑块组织及外周血,提取DNA,采用实时荧光定量PCR (qRT-PCR)的方法检测相对端粒长度,并进行相关性分析.结果 人颈动脉斑块的平均相对端粒长度(Relative telomere length,RTL)为0.56±0.12(平均值±标准差),显著高于外周血白细胞的平均相对端粒长度(0.45±0.13)(P=0.038).多元线性回归方法校正年龄、性别、体重指数、血脂水平、高血压、糖尿病等心血管病危险因素,表明来自同一患者颈动脉斑块组织和外周血白细胞的RTL具有显著的相关性(标化相关系数β=0.87; P=0.0001);外周血白细胞RTL与年龄呈负相关(标化相关系数β=-0.704,P<0.001);颈动脉斑块样本RTL与年龄呈负相关(标化相关系数β=-0.528,P=0.002).结论 人颈动脉斑块组织与外周血白细胞的相对端粒长度具有相关性,外周血白细胞是替代血管组织研究端粒长度与心血管疾病关系的一个重要指标.%Objective To investigate the relationship of relative telomere lengths (RTL) of vascular wall and circulating leukocytes in atherosclerosis patients with carotid endarterectomy. Methods Carotid atherosclerotic plaques and paired blood leukocytes were obtained from 12 patients with atherosclerosis, and relative telomere lengths were measured by real-time quantitative PCR (qRT-PCR). The correlation between the RTLs of two tissues was assessed. Results The average RTL of carotid atherosclerotic plaques (mean ± SD, 0.56 ±0.12) was significantly higher than that of blood leukocytes (0.45 ± 0.13) (P = 0.038). Multivariable linear regression analysis showed a positive association between the telomere lengths

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

    Institute of Scientific and Technical Information of China (English)

    吴德云; 刘迎春; 高宗恩; 李楠; 杨志杰

    2014-01-01

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

  2. 血脂与血管内超声-虚拟组织学评价冠状动脉粥样硬化斑块性质%Correlation between blood lipid and intravascular ultrasound-virtual histology in assessing characteristics of coronary atherosclerotic plaques

    Institute of Scientific and Technical Information of China (English)

    武丽娜; 李新华; 赵晓燕

    2012-01-01

    目的:探讨血脂和血管内超声-虚拟组织(IVUS-VH)学评价急性冠脉综合征(ACS)和稳定性心绞痛(SA)患者冠状动脉粥样硬化斑块性质.方法:对44例ACS患者及22例SA患者行IVUS-VH分析,并对其血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、脂蛋白a [LP(a)]进行测定,计算LDL-C/HDL-C比值,分析冠状动脉粥样硬化斑块坏死核心(NC)所占的比例与LP(a)、LDL-C/HDL-C的相关关系.结果:ACS组斑块中NC和钙化组织比例明显高于SA组(t=4.669、9.894,P<0.001),而纤维组织及纤维脂肪组织则明显低于SA组(t=7.184、5.290,P<0.001).ACS组患者血清LDL-C/HDL-C、LP(a)水平高于SA组患者(t=3.512、19.139,P<0.001).ACS组患者冠状动脉粥样硬化斑块中NC比例与血清LP(a)水平有显著的相关性(r=0.549,P<0.001).结论:LP(a)可能代替IVUS-VH帮助了解冠状动脉粥样硬化斑块的性质.%Aim: To investigate the correlation between blood lipid and intravascular ultrasound-virtual histology(IVUS-VH) in assessing characteristics of the coronary atherosclerotic plaques in patients with acute coronary syndrome(ACS) and stable angina(SA).Methods:The coronary atherosclerotic plaques in 44 patients with ACS and 22 patients with SA were tested by IVUS-VH,and the serum levels of HDL-C,LDL-C and LP(a) were detected. The ratio of LDL-C/HDL-C was calculated.The correlation of the percentage of necrotic core and LP(a),LDL-C/HDL-C was analyzed,respectively.Results:The percentages of necrotic core and dense calcium tissue in ACS were significantly higher than those in SA group (t=4.669,9.894,P<0.001),but the percentages of fibrous tissue and fibro-fatty tissue in ACS were significantly lower than those in SA group(t=7.184,5.290,P<0.001).There were obvious differences in serum level of LP(a) and the ratio of LDL-C/HDL-C between ACS group and SA group (t=3.512,19.139,P<0.001). There was a significant positive correlation between the percentage of necrotic core

  3. CTA analysis of the correlation between the carotid bifurcation angle and the thickness of the internal carotid atherosclerotic plaque%颈动脉分叉角与颈内动脉粥样硬化斑块厚度相关性的 CTA 分析

    Institute of Scientific and Technical Information of China (English)

    周仕恩; 邱传亚; 何汇忱; 许钧杰

    2015-01-01

    Objective To evaluate the correlation between the carotid bifurcation angle and the thickness of the internal carotid atherosclerotic plaque on multi-slice spiral CT angiography (MSCTA).Methods MSCTA images of ninety-nine subjects from 2012 to 2013 were collected and analyzed retrospectively,in which images were processed and analysed with the GE AW4.4 workstation. The common carotid bifurcation angle (CCBA),the internal carotid bifurcation angle (ICBA),the thickness of plaque at the initial region of the internal carotid artery(ICA),and the average diameter of the internal carotid opening were determined.Thickness of atherosclerosis plaque at bilateral carotid bifurcations was grouped based on the CCBA,ICBA and normalized ICBA indexes.The paired T-test (normal distribution)or Wilcoxon sign-ranked test (non-normal distribution)were performed with SPSS version 1 6.0. Association between the CBA and the plaque thickness at the initial region of the ICA were analysed with partial correlation.Statisti-cal significance was set at P 0.05)。偏相关分析示:颈总动脉分叉角分组中,颈总动脉分叉角与颈内动脉斑块厚度间相关系数 r 值为-0.020(P =0.849);颈内动脉分叉角分组中,颈内动脉分叉角与颈内动脉斑块厚度间相关系数 r 值为0.018(P =0.864);颈内动脉分叉角标准化指数分组中,颈内动脉分叉角标准化指数与颈内动脉斑块厚度间相关系数 r 值为0.005(P =0.962)。结论双侧颈动脉分叉角变化不会导致双侧颈内动脉起始部斑块厚度的差异。

  4. Characterization of fracture behavior of human atherosclerotic fibrous caps using a miniature single edge notched tensile test.

    Science.gov (United States)

    Davis, Lindsey A; Stewart, Samantha E; Carsten, Christopher G; Snyder, Bruce A; Sutton, Michael A; Lessner, Susan M

    2016-10-01

    One well-established cause of ischemic stroke is atherosclerotic plaque rupture in the carotid artery. Rupture occurs when a tear in the fibrous cap exposes highly thrombogenic material in the lipid core. Though some fibrous cap material properties have been measured, such as ultimate tensile strength and stress-strain responses, there has been very little, if any, data published regarding the fracture behavior of atherosclerotic fibrous caps. This study aims to characterize the qualitative and quantitative fracture behavior of human atherosclerotic plaque tissue obtained from carotid endarterectomy samples using two different metrics. Uniaxial tensile experiments along with miniature single edge notched tensile (MSENT) experiments were performed on strips of isolated fibrous cap. Crack tip opening displacement (CTOD) and stress in the un-cracked segment (UCS) were measured at failure in fibrous cap MSENT specimens subjected to uniaxial tensile loading. Both CTOD and the degree of crack blunting, measured as the radius of curvature of the crack tip, increased as tearing propagated through the tissue. Higher initial stress in the UCS is significantly correlated with higher collagen content and lower macrophage content in the fibrous cap (ρ=0.77, P=0.009; ρ=-0.64, P=0.047; respectively). Trends in the data show that higher CTOD is inversely related to collagen content, though the sample size in this study is insufficient to statistically substantiate this relationship. To the authors' knowledge, this is the pioneering study examining the fracture behavior of fibrous caps and the first use of the CTOD metric in vascular tissue. A tear in the fibrous cap of atherosclerotic plaque can lead to ischemic stroke or myocardial infarction. While there is some information in the literature regarding quantitative measures of fibrous cap failure, there is little information regarding the behavior of the tissue during failure. This study examines the failure behavior of fibrous

  5. 普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的保护作用及其机制的研究%Investigation of the mechanisms of protective effect of propranolol on the progression of atherosclerotic plaque in rats caused by epinephrine

    Institute of Scientific and Technical Information of China (English)

    周敬群; 周军; 董勇; 曾秋棠; 杨维华

    2011-01-01

    Objective:To investigate the mechanisms of protective effect of propranolol on the progression of atherosclerotic plaque, and to study the changes of expression of CD68 and matrix metalloproteinase 9 (MMP 9) in rats caused by epinephrine. Methods:50 male Wistar rats were fed with high cholesterol diet for 17 weeks to estab lish atherosclerotic model. Then, they were randomly divided into five groups: control group, epinephrine group, propranolol group A, propranolol group B and propranolol group C (10 rats each group). All groups were contin uously fed with high cholesterol diet. At the same time, control group rats were treated with 0. 9% sodium chlo ride 0. 5 ml/d, ih; epinephrine group rats were treated with epinephrine 0. 5 mg/kg ? D, ih; propranolol groups were pretreated with propranolol (group A 2. 5 mg/kg ? D; group B 5 mg/kg ? D; group C 7. 5 mg/kg ? D) before 30 minutes treatment with epinephrine. After one week, the expressions of CD68 and MMP 9 in the artery athero sclerotic plaque were examined by immunohistochemistry. Results: Compared with control group, the expressions of CD68 and MMP 9 in epinephrine group were significantly increased (P<0. 05). Compared with epinephrine group, propranolol groups showed that the expressions of CD68 and MMP 9 in atherosclerotic plaque decreased significantly (P<0. 05). Among propranolol groups, with the increase of the propranolol dose, the positive ex pression of CD68 and MMP 9 were decreased, but no significant difference were observed. Conclusion:Propranolol can delay the progression of atherosclerotic plaque which may due to its effect to attenuate the macrophage infiltra tion and MMP 9 expression induced by epinephrine.%目的:探讨普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的预防作用及其机制.方法:50只Wistar雄性大鼠经高脂喂养17周,制成动脉粥样硬化模型.随机分为对照组、肾上腺素组、普萘洛尔小剂量组、普萘洛尔中剂量组、

  6. Extracellular matrix proteomics identifies molecular signature of symptomatic carotid plaques

    Science.gov (United States)

    Langley, Sarah R.; Willeit, Karin; Didangelos, Athanasios; Matic, Ljubica Perisic; Skroblin, Philipp; Barallobre-Barreiro, Javier; Lengquist, Mariette; Rungger, Gregor; Kapustin, Alexander; Kedenko, Ludmilla; Molenaar, Chris; Lu, Ruifang; Barwari, Temo; Suna, Gonca; Iglseder, Bernhard; Paulweber, Bernhard; Willeit, Peter; Pasterkamp, Gerard; Davies, Alun H.; Monaco, Claudia; Hedin, Ulf; Shanahan, Catherine M.; Willeit, Johann; Kiechl, Stefan

    2017-01-01

    BACKGROUND. The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the “vulnerable plaque,” necessitating an improved approach for predicting onset of symptoms. METHODS. We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques. Proteomics data were integrated with gene expression profiling of 121 carotid endarterectomies and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. Finally, epidemiological validation of candidate biomarkers was performed in two community-based studies. RESULTS. Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study. CONCLUSION. The identified 4-biomarker signature may improve risk prediction and diagnostics for the management of cardiovascular disease. Further, our study highlights the strength of tissue-based proteomics for biomarker discovery. FUNDING. UK: British Heart Foundation (BHF); King’s BHF Center; and the National Institute for Health Research Biomedical Research Center based at Guy’s and St

  7. Quantitative coronary plaque analysis predicts high-risk plaque morphology on coronary computed tomography angiography: results from the ROMICAT II trial.

    Science.gov (United States)

    Liu, Ting; Maurovich-Horvat, Pál; Mayrhofer, Thomas; Puchner, Stefan B; Lu, Michael T; Ghemigian, Khristine; Kitslaar, Pieter H; Broersen, Alexander; Pursnani, Amit; Hoffmann, Udo; Ferencik, Maros

    2017-08-12

    Semi-automated software can provide quantitative assessment of atherosclerotic plaques on coronary CT angiography (CTA). The relationship between established qualitative high-risk plaque features and quantitative plaque measurements has not been studied. We analyzed the association between quantitative plaque measurements and qualitative high-risk plaque features on coronary CTA. We included 260 patients with plaque who underwent coronary CTA in the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) II trial. Quantitative plaque assessment and qualitative plaque characterization were performed on a per coronary segment basis. Quantitative coronary plaque measurements included plaque volume, plaque burden, remodeling index, and diameter stenosis. In qualitative analysis, high-risk plaque was present if positive remodeling, low CT attenuation plaque, napkin-ring sign or spotty calcium were detected. Univariable and multivariable logistic regression analyses were performed to assess the association between quantitative and qualitative high-risk plaque assessment. Among 888 segments with coronary plaque, high-risk plaque was present in 391 (44.0%) segments by qualitative analysis. In quantitative analysis, segments with high-risk plaque had higher total plaque volume, low CT attenuation plaque volume, plaque burden and remodeling index. Quantitatively assessed low CT attenuation plaque volume (odds ratio 1.12 per 1 mm(3), 95% CI 1.04-1.21), positive remodeling (odds ratio 1.25 per 0.1, 95% CI 1.10-1.41) and plaque burden (odds ratio 1.53 per 0.1, 95% CI 1.08-2.16) were associated with high-risk plaque. Quantitative coronary plaque characteristics (low CT attenuation plaque volume, positive remodeling and plaque burden) measured by semi-automated software correlated with qualitative assessment of high-risk plaque features.

  8. Correlation between Carotid Atherosclerotic Plaque and Type H Hypertension in Patients with Ischemic Stroke%缺血性脑卒中患者颈动脉粥样硬化斑块与H型高血压的相关性

    Institute of Scientific and Technical Information of China (English)

    贾蕾; 郭改艳

    2016-01-01

    目的:探讨缺血性脑卒中患者颈动脉粥样硬化斑块与H型高血压的相关性。方法:选取2012年10月~2014年10月期间,我院收治的缺血性脑卒中患者临床资料162份,分为实验组和对照组。实验组为有颈动脉粥样硬化斑块的缺血性脑卒中患者101例,对照组为没有颈动脉粥样硬化斑块的缺血性脑卒中患者61例。采用酶联免疫法对患者的同型半胱氨酸进行检测,并根据检测结果和高血压史将所有的患者分为四种类型,A类为H型高血压患者,B类为普通高血压组患者,C类为高同型半胱氨酸患者,D类为高血压和同型半胱氨酸都正常的患者,分别对实验组和对照组进行四种类型的检测,将两组检测结果进行比较,分析缺血性脑卒中患者颈动脉粥样硬化斑块与H型高血压的相关性。结果:实验组患者在年龄、吸烟史、高血压史、低密度脂蛋白与对照组患者想比较,有显著差异P<0.05,具有统计学意义;实验组患者和对照组患者中四种类型患者有明显的差异,P<0.05,具有统计学意义,且实验组患者中,A类H型高血压患者发生率最高,其次是B类普通高血压组患者,再者就是C类高同型半胱氨酸患者,最后是D类高血压和同型半胱氨酸都正常的患者。结论:H型高血压缺血性脑卒中患者发生颈动脉粥样硬化斑块的概率最高。%Objective: To explore the ischemic stroke patients with carotid atherosclerotic plaque and H the correlation of high blood pressure.Methods: Selection during October 2012 to October 2012, our hospital clinical data of 162 patients with ischemic stroke, divided into the experimental group and the control group, experimental group is in the form of carotid atherosclerotic plaques, 101 cases of ischemic cerebral apoplexy patients and control group with no carotid atherosclerotic plaque of 61 cases of ischemic cerebral apoplexy

  9. 依折麦布辛伐他汀片对兔腹主动脉粥样硬化斑块逆转作用的实验研究%Effects of ezetimibe/simvastatin tablets on atherosclerotic plaque regression of abdominal arteries in rabbits

    Institute of Scientific and Technical Information of China (English)

    于熙滢; 周大亮; 郭颖; 吕建; 魏林; 曹海利

    2014-01-01

    ObjectiveTo observe the efficiency of ezetimibe/simvastatin (ES) tablets on the regression of atherosclerotic plaque of abdominal arteries in rabbits.Methods Twenty-four healthy male New Zealand rabbits were randomly divided into 2 groups: control group (n=8) and hypercholesterolemia group (n=16). Control group was fed with normal diet for 12 weeks. The other group animals were given a cholesterol-supplemented diet (normal diet+15g/L cholesterol+100g/L lard+150g/L egg yolk powder) for 2 weeks, and underwent catheter-induced arterial wall injury. These rabbits were then randomized to model subgroup (n=8, for another 10 weeks of hypercholesterol diet) and ES treatment subgroup [n=8, 5/10mg/(kg·d) for another 10 weeks]. Chinese russell’sviper venom was intra-peritoneally injected to trigger plaque rupture. Abdominal aortagraphy was carried out to measure the aorta stenosis. After 12 weeks’ feeding, all rabbits were sacrificed, and their abdominal arteries were isolated, paraffin-embedded and then sectioned. Blood lipid and lipoproteins were detected. The development of the atherosclerotic plaques was evaluated through the light microscopy. Finally, the expression of macrophage and smooth muscle actin in the abdominal arteries was measured by immunohistochemical analysis.Results The serum levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) were significantly lower in the ES treatment subgroup than in the hypercholesterolemia model group (P<0.01). One-way analysis of variance indicated that significant differences were found in the plaque diameter, plaque thickness and the intimal-medial thickness between the ES subgroup and hypercholesterolemia model subgroup by morphological observation (P<0.05). Immunohistochemical analysis showed that lesser macrophages (P<0.05) but more smooth muscle cells (P<0.01) were found in the ES treatment subgroup than in the model group.Conclusion It may be through reducing the

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

    Science.gov (United States)

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

    2016-08-01

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

  11. 超声和血脂水平检测对颈动脉斑块稳定性诊断的应用%Study on application of ultrasound and blood level of lipids in diagnosis of the stability of atherosclerotic plaque in carotid artery

    Institute of Scientific and Technical Information of China (English)

    于明月; 李红艳; 刘欣; 焦荣红; 薛红元; 牛慧敏; 于明娟

    2014-01-01

    Objective To evaluate the role of ultrasonic elastograsphy and blood levels of lipids in diagnosis of stability of atherosclerotic plaque in carotid artery. Methods Sixty patients diagnosed as cerebral infarction during January 2013 to December 2013 were allocated in obser_vation group and 60 healthy persons taking health examination in outpatient service were allocated in control group for prospective study. All their clinical data and history records were studied according to the actual order one by one,and blood levels of lipids including three acyl glycerin ( TG),total cholesterol( TC),low density lipoprotein cholesterol( LDL-C)and high density lipoprotein cholesterolother( HDL-C)indicators were evaluated,information of carotid plaques had been recorded by using ultrasond combined with UE( ultrasonic elastography). Results Rele_vance ratio of total carotid plaques in observation group was higher( P ﹤0. 05). The total number of cases in two groups with UE scores at 4 or less points was not statistically different,but the number of cases with UE scores at 5 points or higher in observation group was significantly higher than those of control group( P ﹤0. 05). Blood levels of lipids especially the index of LDL-C were also significantly higher in observation group ( P ﹤0. 05). Conclusion Abnormally higher LDL-C lipid indexes mean the instability of atherosclerotic plaques in carotid arteries of patients with cerebral infarction,and application of new type UE combined with technique of traditional ultrasonic imaging can more significantly raise the sensitivity of ultrasonic detection of diseased tissues;and the application of ultrasound and detection of blood levels of lipids have practical clinical significance in demonstration of the stability of carotid plaques in carotid arteries.%目的:评估超声和血脂水平检测对颈动脉斑块稳定性诊断的临床应用价值。方法将2013年1月至2013年12月住院治疗的脑梗死病人60例作为观

  12. Coronary plaque morphology on multi-modality imagining and periprocedural myocardial infarction after percutaneous coronary intervention

    Directory of Open Access Journals (Sweden)

    Akira Sato

    2016-06-01

    Full Text Available Percutaneous coronary intervention (PCI may be complicated by periprocedural myocardial infarction (PMI as manifested by elevated cardiac biomarkers such as creatine kinase (CK-MB or troponin T. The occurrence of PMI has been shown to be associated with worse short- and long-term clinical outcome. However, recent studies suggest that PMI defined by biomarker levels alone is a marker of atherosclerosis burden and procedural complexity but in most cases does not have independent prognostic significance. Diagnostic multi-modality imaging such as intravascular ultrasound, optical coherence tomography, coronary angioscopy, near-infrared spectroscopy, multidetector computed tomography, and magnetic resonance imaging can be used to closely investigate the atherosclerotic lesion in order to detect morphological markers of unstable and vulnerable plaques in the patients undergoing PCI. With the improvement of technical aspects of multimodality coronary imaging, clinical practice and research are increasingly shifting toward defining the clinical implication of plaque morphology and patients outcomes. There were numerous published data regarding the relationship between pre-PCI lesion subsets on multi-modality imaging and post-PCI biomarker levels. In this review, we discuss the relationship between coronary plaque morphology estimated by invasive or noninvasive coronary imaging and the occurrence of PMI. Furthermore, this review underlies that the value of the multimodality coronary imaging approach will become the gold standard for invasive or noninvasive prediction of PMI in clinical practice.

  13. Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice.

    Directory of Open Access Journals (Sweden)

    Aikaterini Tsaousi

    Full Text Available Thelper1 (Th1 lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1 macrophage activation or production of matrix degrading metalloproteinases (MMPs and their tissue inhibitors, TIMPs.We studied the effect of T-bet deletion in apolipoproteinE (ApoE knockout mice fed a high fat diet (HFD or normal chow diet (ND. Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS and brachiocephalic artery (BCA plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1, MMPs-2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3.Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased.

  14. Apopotic gene Bax expression in carotid plaque

    Institute of Scientific and Technical Information of China (English)

    Bao-Zhong MEN; Ding-Biao ZHOU; Huai-Yin SHI; Xiao-Ming ZHANG

    2006-01-01

    The expression of BAX in carotid atherosclerosis and its regulation is far from defined. Objectives To investigate BAX expression in stable/fibrous and instable/vulnerable carotid plaque and its clinical significance. Methods 25 cases of carotid plaque specimens obtained from endarterectomy were divided into two groups, stable/fibrous 14 cases, vulnerable/instable 11 cases; aortic artery and its branches from hepatic transplantation donors 6 case as control. The expression of proapoptotic BAX was detected by immunohistochemistry(IHC), in situ hybridization(ISH) and in situ TdT dUTP nick end labeling (TUNEL). Results 5 cases of BAX ( + ) were detected by ICH and ISH, 4 case of TUNEL ( + ) were detected by TUNEL in stable/fibrous carotid plaque , while 10 cases were BAX ( + )by IHC(P < 0.05) , 11case by ISH and 9 case by TUNEL were detected in instable/vulnerable carotid plaque ( P < 0.01 ), respectively. The intensity of BAX ( + ) cells by IHC and ISH was 8.63 ± 2.62 and 10.32 ± 3.12 in fibrous plaques, whereas 122 ± 21.64and 152 ± 23.35 in vulnerable plaques, respectively. No expression of BAX was found in controlled group. Conclusion The higher expression of Bax in vulnerable carotid plaque may be one mechanisms in molecular pathogenesis of carotid atherosclerosis which affect plaque stability and be the cause of higher incidence of stroke than fibrous carotid plaques, the regulation of BAX expression in different stage of atherosclerosis may provide targets in gene therapy for carotid atherosclerosis.

  15. Differential sensitivity to apoptosis among the cells that contribute to the atherosclerotic disease.

    Science.gov (United States)

    Zeini, Miriam; López-Fontal, Raquel; Través, Paqui G; Benito, Gemma; Hortelano, Sonsoles

    2007-11-16

    Apoptosis plays an important role in a great number of pathological processes, including atherosclerotic disease. Although apoptosis occurs in the major cell types found in atherosclerotic lesions (e.g. macrophages, endothelial cells, and smooth muscle cells), the mechanism involved in this process differs depending on the stage, the localization and the cell composition of the plaque. In this study, we have compared the effects of different apoptotic inducers on the cells that form the atherosclerotic plaque. We have demonstrated that monocytes and macrophages are more susceptible to apoptosis than smooth muscle cells and endothelial cells. These findings provide insights about the potential role of apoptosis in the atherosclerotic disease and suggest strategies to treat vascular diseases by exploiting the differential sensitivity of cells to cell death.

  16. Rationale and design of the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry: A comprehensive exploration of plaque progression and its impact on clinical outcomes from a multicenter serial coronary computed tomographic angiography study.

    Science.gov (United States)

    Lee, Sang-Eun; Chang, Hyuk-Jae; Rizvi, Asim; Hadamitzky, Martin; Kim, Yong-Jin; Conte, Edoardo; Andreini, Daniele; Pontone, Gianluca; Volpato, Valentina; Budoff, Matthew J; Gottlieb, Ilan; Lee, Byoung Kwon; Chun, Eun Ju; Cademartiri, Filippo; Maffei, Erica; Marques, Hugo; Leipsic, Jonathon A; Shin, Sanghoon; Choi, Jung Hyun; Chung, Namsik; Min, James K

    2016-12-01

    The natural history of coronary artery disease (CAD) in patients with low-to-intermediate risk is not well characterized. Although earlier invasive serial studies have documented the progression of atherosclerotic burden, most were focused on high-risk patients only. The PARADIGM registry is a large, prospective, multinational dynamic observational registry of patients undergoing serial coronary computed tomographic angiography (CCTA). The primary aim of PARADIGM is to characterize the natural history of CAD in relation to clinical and laboratory data. The PARADIGM registry (ClinicalTrials.govNCT02803411) comprises ≥2,000 consecutive patients across 9 cluster sites in 7 countries. PARADIGM sites were chosen on the basis of adequate CCTA volume, site CCTA proficiency, local demographic characteristics, and medical facilities to ensure a broad-based sample of patients. Patients referred for clinically indicated CCTA will be followed up and enrolled if they had a second CCTA scan. Patients will also be followed up beyond serial CCTA performance to identify adverse CAD events that include cardiac and noncardiac death, myocardial infarction, unstable angina, target vessel revascularization, and CAD-related hospitalization. The results derived from the PARADIGM registry are anticipated to add incremental insight into the changes in CCTA findings in accordance with the progression or regression of CAD that confer prognostic value beyond demographic and clinical characteristics. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  18. Correlation between carotid artery vulnerable plaques and recurrent ischemic cerebral stroke%颈动脉易损斑块与缺血性脑卒中复发的相关性研究

    Institute of Scientific and Technical Information of China (English)

    刘国荣; 王大力; 张文丽; 安亚臣; 郑德松; 姚林

    2012-01-01

    目的 对颈动脉斑块进行评价,分析斑块性质、形态及其危险因素与缺血性脑卒中复发的相关性.方法 选择经头颅CT和(或)MRI确诊为缺血性脑卒中复发患者209例,应用CT血管造影联合彩色多普勒超声检查证实122例有颈动脉斑块,根据斑块性质分为易损斑块组86例,稳定斑块组36例,分析斑块性质、形态,观察发生缺血性脑血管事件相关因素,比较2组缺血性脑卒中复发的时间、分布及狭窄的关系,Cox风险比例模型分析缺血性脑卒中复发与颈动脉斑块等危险因素间的相关性.结果 209例患者中,颈动脉斑块122例,占58.4%.与稳定斑块组比较,易损斑块组年龄更高,高血压和冠心病的比例更多(P<0.05).Cox回归分析显示,易损斑块与冠心病是缺血性脑卒中复发的危险因素.结论 颈动脉斑块性质、形态和冠心病是缺血性脑卒中复发的危险因素.%Objective To assess the carotid artery plaques (CAP) and analyze the correlation of their nature, morphology and risk factors with recurrent ischemic cerebral stroke. Methods Of the 209 patients with recurrent ischemic cerebral stroke established by head CT and/or MRI in this study, 122 were diagnosed with CAP by combined CT angiography and carotid artery ultra-sonography,86 were diagnosed with vulnerable CAP and 36 were diagnosed with stable CAP according to their nature. The nature and morphology of CAP were analyzed and related factors for ischemic cerebrovascular events were observed. Relation of recurrent time of vulnerable and non-vulnerable ischemic ischemic cerebrovascular events with their distribution and stenosis was compared. Correlation between recurrent ischemic cerebrovascular events and risk factors for CAP was analyzed using the Cox risk model. Results CAP were detected in 122 patients(58. 4%). The age of patients with stable CAP was higher than that of those with vulnerable CAP. The proportion of hypertention and coronary

  19. 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...

  20. 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...

  1. 急性缺血性脑卒中患者血清氧化型低密度脂蛋白水平与颈动脉易损斑块的关系%Relationship Between Serum Oxidized Low-density Lipoprotein Level and Carotid Vulnerable Plaque in Patients with Acute Cerebral Ischemic Stroke

    Institute of Scientific and Technical Information of China (English)

    许寅宏; 徐恩; 林清原; 邱少东

    2015-01-01

    PurposeTo investigate the relationship between the serum oxidized low-density lipoprotein (ox-LDL) level and carotid vulnerable plaque in patients with acute cerebral ischemic stroke, and to evaluate the ability of serum ox-LDL in identifying vulnerable carotid plaques.Materials and Methods 181 patients with history of acute cerebral ischemic stroke were recruited. According to the results of carotid ultrasound patients were divided into non plaque group (n=48), stable plaque group (n=38) and vulnerable plaque group (n=95). The serum total cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, fasting plasma glucose and ox-LDL were measured. Carotid intima-medial thickness (CIMT), total carotid plaque area (TPA) and the characters of plaque were examined with color Doppler ultrasound.Results The serum ox-LDL and the number of patients with hypertension in plaque group were significantly higher than that in the non-plaque group (P<0.05). The serum ox-LDL and TPA in the vulnerable plaque group were significantly higher than that in the stable plaque group (P<0.05). Serum ox-LDL in patients with acute cerebral infarction was positively correlated with CIMT, serum total cholesterol and LDL-C (r1=0.154,P<0.05;r2=0.338, P<0.05;r3=0.385,P<0.05). Logistic regression analysis showed that serum ox-LDL was an independent risk factor for carotid vulnerable plaque (OR=1.038, 95%CI 1.008-1.069, P<0.01).Conclusion The serum ox-LDL is independently associated with the formation of vulnerable plaque in patients with acute cerebral infarction. This study suggests that ox-LDL can be used as a biomarker in screening for vulnerable carotid plaque in clinical practice. Carotid ultrasound combined with serology can early identify carotid artery vulnerable plaque that may lead to cerebral ischemic events.%目的:探讨急性缺血性脑卒中患者血清氧化型低密度脂蛋白(ox-LDL)水平与颈动脉易损斑块的关系,评

  2. Molecular mechanism study of intervention effect of Cassia seed on atherosclerotic plaque of rab-bits with hyperhomocysteinemia%决明子对高同型半胱氨酸血症兔动脉粥样斑块干预的分子机制研究

    Institute of Scientific and Technical Information of China (English)

    周路坦; 周玲生; 周银生; 丁可

    2014-01-01

    Objective To investigate the molecular mechanism of intervention effect of Cassia seed on atherosclerotic plaque of rabbits with hyperhomocysteinemia. Methods Forty rabbits were ran-domly divided into four groups:control group, methionine group,Cassia seed ﹢ methionine group,Lipitor﹢methionine group. Rabbits with hyperhomocysteinemia model were established using high L-methionine. The plasma levels of homocysteine( Hcy)in rabbits were compared among the four groups. The formation process of plaque was detected by vascular ultrasound,the expression levels of Bcl-2 and Bax were observed by immunohistochemistry,and the intervention effect of Cassia seed on the pathologic process of the disease was analyzed. Results Compared with methionine group,IMT of ab-dominal aorta and Vp of abdominal aorta decreased obviously in Cassia seed group and Lipitor group, there were significant differences( P ﹤0. 05 ),but there were no significant differences between Cassia seed group and Lipitor group( P ﹥0. 05 ). Immunohistochemistry showed that,there was significant difference in the Bax expression level between methionine group and control group( P﹤0. 01 ). Compared with methionine group,the positive expression rate of Bax in smooth muscle cells and foam cells de-creased,the expression levels of Bcl-2 increased slightly in Cassia seed group and Lipitor group,there were significant differences(P﹤0. 01). The ratio of Bax/Bcl-2 decreased in Cassia seed group. Conclu-sions Cassia seed can intervene the formation of atherosclerotic plaque of rabbits with hyperhomocys-teinemia through down-regulation the ratio of Bax/Bcl-2 .%目的:探讨决明子对高同型半胱氨酸( HHcy)血症兔动脉粥样斑块干预的分子机制。方法将40只家兔随机分成对照组、蛋氨酸组、决明子﹢蛋氨酸组、立普妥﹢蛋氨酸组。采用高L-蛋氨酸建立兔高同型半胱氨酸血症模型。比较各组兔血浆同型半胱氨酸( Hcy)含量,应用血

  3. Arterial calcification: Conscripted by collagen

    Science.gov (United States)

    Miller, Jordan D.

    2016-03-01

    In atherosclerotic plaques, patterns of calcification -- which have profound implications for plaque stability and vulnerability to rupture -- are determined by the collagen's content and patterning throughout the plaque.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Through several observational and mechanistic studies, microbial infection is known to promote cardiovascular disease. Direct infection of the vessel wall, along with the cardiovascular risk factors, is hypothesized to play a key role in the atherogenesis by promoting an inflammatory ...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Elevated levels of the heme enzyme myeloperoxidase (MPO) are associated with adverse cardiovascular outcomes. MPO predominantly catalyzes formation of the oxidants hypochlorous acid (HOCl) from Cl(-), and hypothiocyanous acid (HOSCN) from SCN(-), with these anions acting as competitive substrates....... HOSCN is a less powerful and more specific oxidant than HOCl, and selectively targets thiols; such damage is largely reversible, unlike much HOCl-induced damage. We hypothesized that increased plasma SCN(-), and hence HOSCN formation instead of HOCl, may decrease artery wall damage. This was examined...... using high-fat fed atherosclerosis-prone LDLR(-/-) mice transgenic for human MPO, with and without SCN(-) (10 mM) added to drinking water. Serum samples, collected fortnightly, were analyzed for cholesterol, triglycerides, thiols, MPO, and SCN(-); study-long exposure was calculated by area under...

  6. Fluorescence spectrum analysis of atherosclerotic plaque using doxycycline.

    Science.gov (United States)

    Miyagi, M; Nakajima, H; Katoh, T; Usui, M; Amemiya, T; Nagai, Y; Ibukiyama, C

    1999-05-01

    Using doxycycline (DOXY), fluorescence spectrum analysis was performed on arteriosclerotic lesions, and the efficacy of this method was examined in basic and clinical studies. In the basic study, DOXY 50 mg was administered intravenously to arteriosclerotic rabbits, and the thoracoabdominal aorta removed. Fluorescence spectral analysis was performed on each specimen, and the fluorescence spectral pattern, peak intensity and degree of intimal hypertrophy were studied. In the clinical study, DOXY 200 mg was administered intravenously to 6 human subjects with stable angina and coronary arterial stenosis of greater than 90%, and coronary angiography, coronary angioscopy and fluorescence spectral analysis were performed. DOXY accumulation in the arteriosclerotic intima of rabbit aortae was confirmed. The fluorescence spectrum was monomodal, peaking at around 532 nm. In the noncalcification group, significant correlation was observed between peak intensity and arteriosclerotic intimal thickness. Using DOXY as a fluorescent marker, it was possible to assess the level of arteriosclerotic intimal hypertrophy. Clinically, it was possible to obtain the DOXY spectrum of the coronary arteries.

  7. Atherosclerotic plaque and shear stress in cartotid arteries

    NARCIS (Netherlands)

    H.C. Groen (Harald)

    2010-01-01

    textabstractThe human is a very sophisticated organism in which adaptation is the key to its survival. During a lifetime, the human body is exposed to a wide variety of stimuli. Some of them are self-inflicted while others arise from the environment and nature itself. Communication plays an importan

  8. Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

    Directory of Open Access Journals (Sweden)

    Sara Hägg

    Full Text Available BACKGROUND: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric (14C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s to determine the average biological age of carotid plaques. METHODOLOGY/PRINCIPAL FINDING: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for (14C content by accelerator mass spectrometry. The average plaque age (i.e. formation time was 9.6±3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014. Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1-5. However, plaques in the lowest tercile of plaque age (most recently formed were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively, less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05, and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05 than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our results show, for the first time, that plaque age, as judge by relative incorporation of (14C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.

  9. SilverHawk斑块切除治疗动脉粥样硬化导致的下肢缺血14例报告%Plaque Excision with SilverHawk Treating Atherosclerotic Lower Extremity Ischemia: Report of 14 Cases

    Institute of Scientific and Technical Information of China (English)

    谷涌泉; 汪忠镐; 郭连瑞; 齐立行; 李学锋; 崔世军; 佟铸; 吴英锋; 郭建明; 张建

    2011-01-01

    Objective To explore the safety and efficacy of endovascular plaque excision with SilverHawk. Methods Clinical data of 14 patients with atherosclerotic lower extremity ischemia, who received SilverHawk plaque excision, were retrospectively analyzed. In the patients, excision of the hyperplastic arterial intema was done in 9 patients with poststenting arterial restenosis or occlusion; simple plaque excision in the lower extremity was made in the other 5. Ipsilateral antegrade femoral artery puncture was carried out in 6 patients; contralateral retrograde femoral artery puncture was done in 6 patients; puncture in the left axilliary artery was made in 1 patient; retrograde femoral artery puncture was made in 1 patient. Results All the operations were completed successfully, and all the patients were discharged with patent recanalized artery. Claudication distance increased to more than 300 meters in the 7 patients who had the symptom, and rest pain was relieved in all the 5 patients who suffered from it. In one patient, who had toe ulcer, the size of the ulcer decreased from 3 cm ×4 cm to 2 cm ×2 cm; and in the other one, who had necrosis, the lesion was dry at discharge from hospital. Postoperative ABI was 0.7-0. 8 in 4 patients, 0. 81 -0. 9 in 4, and >0.91 in 6. The patients were followed up for 1-5 months ( mean ,3.5 months) , during which one of them had recurrent intermittent claudication in four months; the case of necrosis received amputation because of foot osteomyelitis; one patient had the ulcer healed; no recurrent rest pain was complained. Conclusions Plaque excision with SilverHawk is safe and effective. Further follow-up is necessary to confirm its long-term efficacy.%目的 探讨SilverHawk斑块切除术的安全性和有效性. 方法 2010年10月~2011年4月对14例动脉粥样硬化导致的下肢缺血施行SilverHawk斑块切除,支架后再闭塞或狭窄内膜切除9例,单纯下肢动脉斑块切除5例.采用同侧顺行股动脉穿刺6

  10. Intracranial Atherosclerotic Disease

    Directory of Open Access Journals (Sweden)

    Maria Khan

    2011-01-01

    Full Text Available Intracranial atherosclerotic disease (ICAD is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%–99% stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population.

  11. Surface-Functionalized Nanoparticles by Olefin Metathesis: A Chemoselective Approach for In Vivo Characterization of Atherosclerosis Plaque.

    Science.gov (United States)

    Salinas, Beatriz; Ruiz-Cabello, Jesús; Lechuga-Vieco, Ana V; Benito, Marina; Herranz, Fernando

    2015-07-13

    The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well-defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanoparticles with three different examples. This approach enables, in one step, the synthesis and functionalization of different water-stable magnetite-based particles from oleic acid-coated counterparts. The surface of the nanoparticles was completely characterized showing how the metathesis approach introduces a large number of hydrophilic molecules on their coating layer. As an example of the possible applications of these new nanocomposites, a focus was taken on atherosclerosis plaques. It is also demonstrated how the in vitro properties of one of the probes, particularly its Ca(2+) -binding properties, mediate their final in vivo use; that is, the selective accumulation in atherosclerotic plaques. This opens promising new applications to detect possible microcalcifications associated with plaque vulnerability. The accumulation of the new imaging tracers is demonstrated by in vivo magnetic resonance imaging of carotids and aorta in the ApoE(-/-) mouse model and the results were confirmed by histology.

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

    Science.gov (United States)

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

    1994-07-01

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

  13. Self-gated CINE MRI for combined contrast-enhanced imaging and wall-stiffness measurements of murine aortic atherosclerotic lesions.

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    Brigit den Adel

    Full Text Available BACKGROUND: High-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent. METHODS AND RESULTS: We applied a 2D-FLASH retrospective-gated CINE MRI method at 9.4T to characterize atherosclerotic plaques and vessel wall distensibility in the aortic arch of aged ApoE(-/- mice after injection of a contrast agent. The method enabled detection of contrast enhancement in atherosclerotic plaques in the aortic arch after I.V. injection of micelles and iron oxides resulting in reproducible plaque enhancement. Both contrast agents were taken up in the plaque, which was confirmed by histology. Additionally, the retrospective-gated CINE method provided images of the aortic wall throughout the cardiac cycle, from which the vessel wall distensibility could be calculated. Reduction in plaque size by statin treatment resulted in lower contrast enhancement and reduced wall stiffness. CONCLUSIONS: The retrospective-gated CINE MRI provides a robust and simple way to detect and quantify contrast enhancement in atherosclerotic plaques in the aortic wall of ApoE(-/- mice. From the same scan, plaque-related changes in stiffness of the aortic wall can be determined. In this mouse model, a correlation between vessel wall stiffness and atherosclerotic lesions was found.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  15. Cognitive functioning and quality of life of atherosclerotic patients following carotid endarterectomy.

    NARCIS (Netherlands)

    Bossema, E.R.; Brand, A.N.; Moll, F.L.; Ackerstaff, R.G.A.; Doornen, L.J.P. van

    2002-01-01

    Background: Carotid endarterectomy (CEA) is a surgical procedure to remove atherosclerotic plaque from one of the carotid arteries in patients with severe stenosis. The purpose is to prevent future cerebral ischemic attacks. Whether patients, in addition, improve in cognitive functions and quality o

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Experience With Intravascular Ultrasound Imaging Of Human Atherosclerotic Arteries

    Science.gov (United States)

    Mallery, John A.; Gessert, James M.; Maciel, Mario; Tobis, John M.; Griffith, James M.; Berns, Michael W.; Henry, Walter L.

    1989-08-01

    Normal human arteries have a well-defined structure on intravascular images. The intima appears very thin and is most likely represented by a bright reflection arising from the internal elastic lamina. The smooth muscle tunica media is echo-lucent on the ultrasound image and appears as a dark band separating the intima from the adventitia. The adventitia is a brightly reflective layer of variable thickness. The thickness of the intima, and therefore of the atherosclerotic plaque can be accurately measured from the ultrasound images and correlates well with histology. Calcification within the wall of arteries is seen as bright echo reflection with shadowing of the peripheral wall. Fibrotic regions are highly reflective but do not shadow. Necrotic liquid regions within advanced atherosclerotic plaques are seen on ultrasound images as large lucent zones surrounded by echogenic tissue. Imaging can be performed before and after interventional procedures, such as laser angioplasty, balloon angioplasty and atherectomy. Intravascular ultrasound appears to provide an imaging modality for identifying the histologic characteristics of diseased arteries and for quantifying plaque thickness. It might be possible to perform such quantification to evaluate the results of interventional procedures.

  20. The unstable plaque: a diagnostic challenge in cardiology; Diagnostische Herausforderung in der Kardiologie: Die instabile arteriosklerotische Plaque

    Energy Technology Data Exchange (ETDEWEB)

    Levkau, B. [Inst. fuer Pathophysiologie, Universitaetsklinikum Essen (Germany); Schaefers, M. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Muenster (Germany)

    2004-09-01

    Atherosclerotic plaque rupture still accounts for one third of all deaths worldwide and constitutes a major source of disability and health care costs. Dysregulation of MMPs in the atherosclerotic lesion may result in mechanical destabilization and rupture of the atherosclerotic plaque, potentially leading to thrombosis and vessel occlusion with life-threatening clinical complications. Therefore, identifying individual patients at high risk of plaque rupture is an important challenge in clinical medicine. We have used the broad-spectrum MMP inhibitor CGS 27023A to develop the radioligand [{sup 123}I]I-HO-CGS 27023A for in vivo imaging of MMP activity. Using this radioligand, we were able to specifically image MMP activity by scintigraphy in vivo in the MMP-rich vascular lesions that develop after carotid artery ligation and cholesterol-rich diet in apolipoprotein E-deficient mice. Thus, imaging of MMP activity in vivo is feasible using radiolabelled MMP inhibitors. In combination with the high-resolution morphological imaging techniques such as MRI and CT, the molecular imaging of individual disease parameters such as MMP activity in lesions of atherosclerosis may help design approaches for the prediction and prevention of coronary events due to plaque rupture of an individual lesion in an individual patient. (orig.)

  1. Adventitial inflammation and its interaction with intimal atherosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Mohammadreza eAkhavanpoor

    2014-08-01

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

  2. A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis.

    Science.gov (United States)

    van Dijk, R A; Duinisveld, A J F; Schaapherder, A F; Mulder-Stapel, A; Hamming, J F; Kuiper, J; de Boer, O J; van der Wal, A C; Kolodgie, F D; Virmani, R; Lindeman, J H N

    2015-03-26

    Experimental studies characterize adaptive immune response as a critical factor in the progression and complications of atherosclerosis. Yet, it is unclear whether these observations translate to the human situation. This study systematically evaluates cellular components of the adaptive immune response in a biobank of human aortas covering the full spectrum of atherosclerotic disease. A systematic analysis was performed on 114 well-characterized perirenal aortic specimens with immunostaining for T-cell subsets (CD3/4/8/45RA/45RO/FoxP3) and the Th1/non-Th1/Th17 ratio (CD4(+)T-bet(+)/CD4(+)T-bet(-)/CD4(+)/interleukin-17(+) double staining). CD20 and CD138 were used to identify B cells and plasma cells, while B-cell maturation was evaluated by AID/CD21 staining and expression of lymphoid homeostatic CXCL13. Scattered CD4 and CD8 cells with a T memory subtype were found in normal aorta and early, nonprogressive lesions. The total number of T cells increases in progressive atherosclerotic lesions (≈1:5 CD4/CD8 T-cell ratio). A further increase in medial and adventitial T cells is found upon progression to vulnerable lesions.This critical stage is further hallmarked by de novo formation of adventitial lymphoidlike structures containing B cells and plasma cells, a process accompanied by transient expression of CXCL13. A dramatic reduction of T-cell subsets, disappearance of lymphoid structures, and loss of CXCL13 expression characterize postruptured lesions. FoxP3 and Th17 T cells were minimally present throughout the atherosclerotic process. Transient CXCL13 expression, restricted presence of B cells in human atherosclerosis, along with formation of nonfunctional extranodal lymphoid structures in the phase preceding plaque rupture, indicates a "critical" change in the inflammatory footprint before and during plaque destabilization. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  3. Silence of TRIB3 Suppresses Atherosclerosis and Stabilizes Plaques in Diabetic ApoE−/−/LDL Receptor−/− Mice

    Science.gov (United States)

    Wang, Zhi-hao; Shang, Yuan-yuan; Zhang, Shun; Zhong, Ming; Wang, Xu-ping; Deng, Jing-ti; Pan, Jie; Zhang, Yun; Zhang, Wei

    2012-01-01

    Insulin resistance triggers the developments of diabetes mellitus and atherosclerosis. Tribbles homolog 3 (TRIB3) is involved in insulin resistance. We aimed to investigate whether TRIB3 is implicated in diabetic atherosclerosis. Sixty 3-week-old apolipoprotein E (ApoE−/−)/LDR receptor (LDLR−/−) mice were randomly divided into chow and diabetes groups. Diabetes was induced by a high-fat and high-sugar diet combined with low-dose streptozotocin. Mice in both groups were randomly divided into vehicle and TRIB3-silencing groups. After transfection, all mice were killed to evaluate the effects of TRIB3 on atherosclerosis. Silence of TRIB3 markedly decreased insulin resistance (P = 0.039) and glucose (P = 0.019), regardless of diabetes. Ultrasonography-measured parameters were similar in both groups, with and without silence of TRIB3. However, silence of TRIB3 decreased the aortic atherosclerotic burden (P = 1 × 10−13). Further study showed that in brachiocephalic lesions, fibrous cap thickness, cap-to-core ratio, collagen content, and the number of smooth muscle cells were significantly increased (P silence of TRIB3, whereas lipid and macrophage contents remained unaltered, with the vulnerability index significantly reduced. Moreover, the numbers of apoptotic cells and macrophages in brachiocephalic lesions were both significantly decreased (P Silence of TRIB3 would diminish atherosclerotic burden and increase the plaque stability in diabetic mice. PMID:22275087

  4. Silence of TRIB3 suppresses atherosclerosis and stabilizes plaques in diabetic ApoE-/-/LDL receptor-/- mice.

    Science.gov (United States)

    Wang, Zhi-hao; Shang, Yuan-yuan; Zhang, Shun; Zhong, Ming; Wang, Xu-ping; Deng, Jing-ti; Pan, Jie; Zhang, Yun; Zhang, Wei

    2012-02-01

    Insulin resistance triggers the developments of diabetes mellitus and atherosclerosis. Tribbles homolog 3 (TRIB3) is involved in insulin resistance. We aimed to investigate whether TRIB3 is implicated in diabetic atherosclerosis. Sixty 3-week-old apolipoprotein E (ApoE-/-)/LDR receptor (LDLR-/-) mice were randomly divided into chow and diabetes groups. Diabetes was induced by a high-fat and high-sugar diet combined with low-dose streptozotocin. Mice in both groups were randomly divided into vehicle and TRIB3-silencing groups. After transfection, all mice were killed to evaluate the effects of TRIB3 on atherosclerosis. Silence of TRIB3 markedly decreased insulin resistance (P=0.039) and glucose (P=0.019), regardless of diabetes. Ultrasonography-measured parameters were similar in both groups, with and without silence of TRIB3. However, silence of TRIB3 decreased the aortic atherosclerotic burden (P=1×10(-13)). Further study showed that in brachiocephalic lesions, fibrous cap thickness, cap-to-core ratio, collagen content, and the number of smooth muscle cells were significantly increased (Psilence of TRIB3, whereas lipid and macrophage contents remained unaltered, with the vulnerability index significantly reduced. Moreover, the numbers of apoptotic cells and macrophages in brachiocephalic lesions were both significantly decreased (PSilence of TRIB3 would diminish atherosclerotic burden and increase the plaque stability in diabetic mice.

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

    DEFF Research Database (Denmark)

    van Engelen, Arna; de Bruijne, Marleen; Klein, Stefan;

    2011-01-01

    Automatic quantification of carotid artery plaque composition is important in the development of methods that distinguish vulnerable from stable plaques. MRI has shown to be capable of imaging different components noninvasively. We present a new plaque classification method which uses 3D registra...

  6. MMP-1 and MMP-9 regulate epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells.

    Science.gov (United States)

    Rao, Velidi H; Kansal, Vikash; Stoupa, Samantha; Agrawal, Devendra K

    2014-02-01

    Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in the development of myocardial infarction and stroke, are not well defined. Here, we examined the role of epidermal growth factor (EGF)-mediated matrix metalloproteinases (MMP) on the stability of interstitial collagens in vascular smooth muscle cells (VSMCs) isolated from carotid endarterectomy tissues of symptomatic and asymptomatic patients with carotid stenosis. VSMCs isolated from the carotid plaques of both asymptomatic and symptomatic patients were treated with EGF. The MMP-9 activity was quantified by gelatin zymography and the analysis of mRNA transcripts and protein for MMP-9, MMP-1, EGFR and collagen types I, Col I(α1) and collagen type III, Col III(α1) were analyzed by qPCR and immunofluorescence, respectively. The effect of EGF treatment to increase MMP-9 activity and mRNA transcripts for MMP-9, MMP-1, and EGFR and to decrease mRNA transcripts for Col I(α1) and Col III(α1) was threefold to fourfold greater in VSMCs isolated from the carotid plaques of symptomatic than asymptomatic patients. Inhibitors of EGFR (AG1478) and a small molecule inhibitor of MMP-9 decreased the MMP9 expression and upregulated Col I(α1) and Col III(α1) in EGF-treated VSMCs of both groups. Additionally, the magnitude in decreased MMP-9 mRNA and increased Col I(α1) and Col III(α1) due to knockdown of MMP-9 gene with siRNA in EGF-treated VSMCs was significantly greater in the symptomatic group than the asymptomatic group. Thus, a selective blockade of both EGFR and MMP-9 may be a novel strategy and a promising target for stabilizing vulnerable plaques in patients with carotid stenosis.

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