Current techniques for the investigation of vulnerable atherosclerotic plaques

International Nuclear Information System (INIS)

Riou, L.; Broisat, A.; Fagret, D.; Ghezzi, C.

2005-01-01

Atherosclerosis is the single most important contributor to cardiovascular diseases, the leading cause of death in industrialized countries. Atherosclerosis complications such as vulnerable coronary plaque rupture or erosion result in acute coronary events, i.e. myocardial infarction and sudden death. Vulnerable plaques initially develop eccentrically without impeding on the vessel lumen and are therefore not detectable using angiography. New techniques for the investigation of vulnerable plaques are needed to identify and treat vulnerable patients. Invasive techniques require the use of intracoronary probes and are thereby not applicable to large populations of patients. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the most promising invasive modalities. They provide morphological data that could potentially be associated with a more functional approach such as thermography, elasto-graphy, or spectroscopy, Non-invasive techniques are better suited for studying larger populations of patients. Computed tomography is currently used for calcium scoring, but the biological meaning and the prognostic value of this index remain to be fully determined. Non-invasive coronary magnetic resonance imaging (MRI) faces numerous technical challenges, and it essentially provides morphological data. Molecular nuclear imaging offers a great sensitivity and the ability to provide metabolic data about atherosclerotic lesions. New potential tracers of vulnerable plaques are currently being evaluated. Nuclear Medicine should therefore play a major role in the future as a non invasive imaging modality for the assessment of vulnerable atherosclerotic plaques. (author)

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).

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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.

Multicolor fluorescence technique to detect apoptotic cells in advanced coronary atherosclerotic plaques

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C Soldani

2009-06-01

Full Text Available Apoptosis occurring in atherosclerotic lesions has been suggested to be involved in the evolution and the structural stability of the plaques. It is still a matter of debate whether apoptosis mainly involves vascular smooth muscle cells (vSMCs in the fibrous tissue or inflammatory (namely foam cells, thus preferentially affecting the cell-poor lipid core of the atherosclerotic plaques. The aim of the present investigation was to detect the presence of apoptotic cells and to estimate their percentage in a series of atherosclerotic plaques obtained either by autopsy or during surgical atherectomy. Apoptotic cells were identified on paraffinembedded sections on the basis of cell nuclear morphology after DNA staining and/or by cytochemical reactions (TUNEL assay, immunodetection of the proteolytic poly (ADP-ribose polymerase-1 [PARP-1] fragment; biochemical procedures (identifying DNA fragmentation or PARP-1 proteolysis were also used. Indirect immunofluorescence techniques were performed to label specific antigens for either vSMCs or macrophages (i.e., the cells which are most likely prone to apoptosis in atherosclerotic lesions: the proper selection of fluorochrome labeling allowed the simultaneous detection of the cell phenotype and the apoptotic characteristics, by multicolor fluorescence techniques. Apoptotic cells proved to be less than 5% of the whole cell population, in atherosclerotic plaque sections: this is, in fact, a too low cell fraction to be detected by widely used biochemical methods, such as agarose gel electrophoresis of low-molecular-weight DNA or Western-blot analysis of PARP-1 degradation. Most apoptotic cells were of macrophage origin, and clustered in the tunica media, near or within the lipid-rich core; only a few TUNEL-positive cells were labeled for antigens specific for vSMCs. These results confirm that, among the cell populations in atherosclerotic plaques, macrophage foam-cells are preferentially involved in apoptosis

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

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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.

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

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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

2018-02-01

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.

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

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

2017-10-01

Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a cost-effective clinical system by highlighting optimal wavelengths and improving plaque characterization.

Genetic analysis of Porphyromonas gingivalis (fimA), Aggregatibacter actinomycetemcomitans, and red complex in coronary plaque.

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Mahendra, Jaideep; Mahendra, Little; Felix, John; Romanos, Georgios E

2014-08-01

The objective of the present study was to detect the presence of Porphyromonas gingivalis (fimA), Aggregatibacter actinomycetemcomitans, and red complex in the coronary plaque of patients with coronary artery disease. The study population consisted of 51 patients with chronic periodontitis undergoing coronary artery bypass grafting. DNA was extracted from subgingival and coronary atherosclerotic plaque samples. Polymerase chain reaction was used to amplify the part of 16S rRNA gene to detect the presence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis (fimA), Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, Porphyromonas gingivalis (fimA), and Treponema denticola were detected in 0%, 31.4%, 45.1%, 39.2%, and 51% of the atherosclerotic plaque samples, respectively. In both subgingival and coronary atherosclerotic plaque samples, Tannerella forsythia was detected in 19.6%, Porphyromonas gingivalis in 39.2%, Porphyromonas gingivalis (fimA) in 33.3%, and Treponema denticola in 35.3% of the samples. The study confirmed the detection of red complex bacteria in coronary plaque samples. However Aggregatibacter actinomycetemcomitans could not be detected in these samples. © 2013 Wiley Publishing Asia Pty Ltd.

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

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Xie S

2009-01-01

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

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

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Ivanović Miloš

2013-01-01

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

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

DEFF Research Database (Denmark)

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

2010-01-01

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

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)

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

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Thorarinn A Bjarnason

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

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)

Relationship between left main coronary artery plaque burden and nonleft main coronary atherosclerosis: results from the PROSPECT study.

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Shimizu, Takehisa; Mintz, Gary S; De Bruyne, Bernard; Farhat, Naim Z; Inaba, Shinji; Cao, Yang; Marso, Steven P; Weisz, Giora; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

2018-05-17

Whether the severity of left main coronary artery (LMCA) disease reflects LMCA and overall coronary atherosclerotic burden is not known. We aimed to assess nonculprit LMCA disease characteristics and the relationship with atherosclerosis in the rest of the coronary arteries as well as patient outcomes. In the PROSPECT study, 697 patients with acute coronary syndromes underwent three-vessel gray-scale and radiofrequency intravascular ultrasound after percutaneous coronary intervention. Overall, 552 patients with adequate LMCA imaging were compared according to LMCA plaque burden. The tertile with the highest plaque burden in the LMCA had the smallest LMCA minimum lumen area (17.4, 14.2, 10.5, lowest through highest tertiles, respectively, PPROSPECT predictors of future nonculprit major adverse cardiac events (MACE) (minimum lumen area≤4 mm, plaque burden≥70%, and virtual histology thin-cap fibroatheroma), the tertile with the highest LMCA plaque burden had the highest number of patients with at least one of three PROSPECT predictors (P=0.03). In multivariable model, though total atheroma volume (per 1%) was an independent predictor of all MACE [hazard ratio (95% confidence interval)=1.06 (1.01-1.11), P=0.02] and strong trend for non-culprit-related MACE [hazard ratio (95% confidence interval)=1.06 (1.00-1.13), P=0.06], plaque burden at LMCA was not (all MACE, P=0.90, non-culprit-related MACE, P=0.85). The severity of atherosclerosis in LMCA predicted the overall atherosclerotic plaque burden as well as the presence of high-risk plaques in the three major epicardial coronary arteries.

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

International Nuclear Information System (INIS)

Dimastromatteo, Julien

2010-01-01

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

[Qualitative and quantitative diagnostic performance of 320-slice computed tomography for detecting coronary artery disease with respect to atherosclerotic plaque characteristics].

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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

3D Fiber Orientation in Atherosclerotic Carotid Plaques

NARCIS (Netherlands)

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

2017-01-01

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

Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile.

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Merghani, Ahmed; Maestrini, Viviana; Rosmini, Stefania; Cox, Andrew T; Dhutia, Harshil; Bastiaenan, Rachel; David, Sarojini; Yeo, Tee Joo; Narain, Rajay; Malhotra, Aneil; Papadakis, Michael; Wilson, Mathew G; Tome, Maite; AlFakih, Khaled; Moon, James C; Sharma, Sanjay

2017-07-11

Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P =0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01-1.15; P =0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC

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

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Bert Rutten

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

High-Risk Coronary Plaques Complicated with Acute Coronary Syndrome in Young Patients

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Opincariu Diana

2017-06-01

Full Text Available Coronary computed tomography angiography (CCTA has evolved notably over the last decade, gaining an increased amount of temporo-spatial resolution in combination with decreased radiation exposure. The importance of CCTA is emerging especially in vulnerable and young patients who might not have developed a viable collateral vascular network to sustain the circulation to an infarction area during a major adverse coronary event. There are a few well-known markers by which a vulnerable plaque can be assessed and that can predict the subsequent events of sudden myocardial ischemia, such as an increased positive remodeling index (cut-off >1.4, low-attenuation plaque (cut-off 0.7, and napkin-ring sign (NRS. This manuscript presents a series of 3 clinical cases of young patients experiencing symptoms and signs of myocardial ischemia who underwent CCTA in order to assess the composition and functional characteristics of atherosclerotic plaques and their repercussion in developing an acute coronary syndrome.

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

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Leon J Schurgers

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

SMARTool: A tool for clinical decision support for the management of patients with coronary artery disease based on modeling of atherosclerotic plaque process.

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Sakellarios, Antonis I; Rigas, George; Kigka, Vassiliki; Siogkas, Panagiotis; Tsompou, Panagiota; Karanasiou, Georgia; Exarchos, Themis; Andrikos, Ioannis; Tachos, Nikolaos; Pelosi, Gualtriero; Parodi, Oberdan; Fotiaids, Dimitrios I

2017-07-01

SMARTool aims to the development of a clinical decision support system (CDSS) for the management and stratification of patients with coronary artery disease (CAD). This will be achieved by performing computational modeling of the main processes of atherosclerotic plaque growth. More specifically, computed tomography coronary angiography (CTCA) is acquired and 3-dimensional (3D) reconstruction is performed for the arterial trees. Then, blood flow and plaque growth modeling is employed simulating the major processes of atherosclerosis, such as the estimation of endothelial shear stress (ESS), the lipids transportation, low density lipoprotein (LDL) oxidation, macrophages migration and plaque development. The plaque growth model integrates information from genetic and biological data of the patients. The SMARTool system enables also the calculation of the virtual functional assessment index (vFAI), an index equivalent to the invasively measured fractional flow reserve (FFR), to provide decision support for patients with stenosed arteries. Finally, it integrates modeling of stent deployment. In this work preliminary results are presented. More specifically, the reconstruction methodology has mean value of Dice Coefficient and Hausdorff Distance is 0.749 and 1.746, respectively, while low ESS and high LDL concentration can predict plaque progression.

Association between epicardial fat volume and coronary plaques diagnosed by multislice computed tomography

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José A. Morán Quijada

2016-01-01

Full Text Available Introduction: Coronary atherosclerotic disease is a major cause of death in Cuba and elsewhere. The volume of epicardial fat is considered a new cardiovascular risk factor because of its association with coronary atherogenesis.Objective: To determine, by multislice computed tomography, the association between epicardial fat volume and the presence of coronary atherosclerotic plaques.Method: A descriptive study was conducted with a universe of 130 patients with chest pain suggestive of ischemic heart disease, of which 117 were selected by opinion sampling. These patients underwent a calcium score study, a coronary angiography and a measurement of the epicardial fat volume.Results: Male patients predominated (54.7% and those aged 60-69 years (32.5%. A high volume of epicardial fat was found in 51.3% of patients, affecting 52.8% of women; 78.9% of patients with a calcium score between 100 and 399 UH had a high volume of epicardial fat, just as 71.2% of those with plaques and 100% of those with 4 or 5 plaques; 41% of patients had various types of plaque, which were mainly located in the anterior descending artery (88.1%.Conclusions: The measurement of the volume of epicardial fat is a useful tool to estimate the presence of coronary disease. When it was high, it was associated with older age, female gender and the presence of a higher calcium score, more plaques, more injuries and a greater involvement of the anterior descending artery.

PET/CT for atherosclerotic plaque imaging

International Nuclear Information System (INIS)

Ben-Haim, S.; Technion Institute of Technology, Haifa; Israel, O.; Rambam Medical Center, Haifa

2006-01-01

Atherosclerosis is one of the leading causes of morbidity and mortality in the world. Rupture of atherosclerotic plaques and thrombi formation are the primary mechanisms of myocardial infarction or cerebrovascular accident. Angiography is considered to represent the gold standard technique for imaging of the arterial lumen. However, in recent years it has been realized that the primary determinant of the atherosclerotic plaque stability is the composition of the plaque and other imaging modalities have been suggested. The purpose of this review is to briefly summarize the knowledge accumulated to present date regarding the potential role of fluo deoxyglucose imaging in the assessment of atherosclerosis and to compare this modality to additional available imaging approaches for the detection of vulnerable plaques

T1-weighted MRI for the detection of coronary artery plaque haemorrhage

International Nuclear Information System (INIS)

Oei, May Lin; Ozgun, Murat; Seifarth, Harald; Bunck, Alexander; Fischbach, Roman; Heindel, Walter; Maintz, David; Orwat, Stefan; Botnar, Rene

2010-01-01

Hyperintense areas in atherosclerotic plaques on pre-contrast T1-weighted MRI have been shown to correlate with intraplaque haemorrhage. We evaluated the presence of T1 hyperintensity in coronary artery plaques in coronary artery disease (CAD) patients and correlated results with multi-detector computed tomography (MDCT) findings. Fifteen patients with CAD were included. Plaques detected by MDCT were categorised based on their Hounsfield number. T1-weighted inversion recovery (IR) MRI prepared coronary MRI for the detection of plaque and steady-state free-precession coronary MR-angiography for anatomical correlation was performed. After registration of MDCT and MRI, regions of interest were defined on MDCT-visible plaques and in corresponding vessel segments acquired with MRI. MDCT density and MR signal measurement were performed in each plaque. Forty-three plaques were identified with MDCT. With IR-MRI 5/43 (12%) plaques were hyperintense, 2 of which were non-calcified and 3 mixed. Average signal-to-noise and contrast-to-noise ratios of hyperintense plaques were 15.7 and 9.1, compared with 5.6 and 1.2 for hypointense plaques. Hyperintense plaques exhibited a significantly lower CT density than hypointense plaques (63.6 vs. 140.8). There was no correlation of plaque signal intensity with degree of stenosis. T1-weighted IR-MRI may be useful for non-invasive detection and characterisation of intraplaque haemorrhage in coronary artery plaques. (orig.)

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

International Nuclear Information System (INIS)

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

2010-01-01

Purpose: Coronary CT angiography (CCTA) is a high-resolution three-dimensional imaging technique for the evaluation of coronary arteries in suspected or confirmed coronary artery disease (CAD). Coregistration of serial CCTA scans would allow precise superimposition of images obtained at two different points in time, which could aid in recognition of subtle changes and precise monitoring of coronary plaque progression or regression. To this end, the authors aimed at developing a fully automatic nonlinear volume coregistration for longitudinal CCTA scan pairs. Methods: The algorithm combines global displacement and local deformation using nonlinear volume coregistration with a volume-preserving constraint. Histogram matching of intensities between two serial scans is performed prior to nonlinear coregistration with dense nonparametric local deformation in which sum of squared differences is used as a similarity measure. The approximate segmentation of coronary arteries obtained from commercially available software provides initial anatomical landmarks for the coregistration algorithm that help localize and emphasize the structure of interest. To avoid possible bias caused by incorrect segmentation, the authors convolve the Gaussian kernel with the segmented binary coronary tree mask and define an extended weighted region of interest. A multiresolution approach is employed to represent coarse-to-fine details of both volumes and the energy function is optimized using a gradient descent method. The authors applied the algorithm in ten paired CCTA datasets (20 scans in total) obtained within 10.7±5.7 months from each other on a dual source CT scanner to monitor progression of CAD. Results: Serial CCTA coregistration was successful in 9/10 cases as visually confirmed. The global displacement and local deformation of target registration error obtained from four anatomical landmarks were 2.22±1.15 and 1.56±0.74 mm, respectively, and the inverse consistency error of local

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

NARCIS (Netherlands)

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

2009-01-01

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

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

DEFF Research Database (Denmark)

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

Aim: Aging is an important independent risk factor for the inception and maturation of atherosclerotic plaques. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and molecular calcification. Methods: Thirteen healthy volunteers without traditional......SUV) [Mean SUVAORTA - Mean SUVBLOOD POOL]. Furthermore, the average maximum 18F-NaF cSUV was determined in the coronary arteries. Calculating regression and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18F-FDG avidity. A second order...... polynomial regression established that aging is a strong predictor of the degree of aortic plaque inflammation (R2 = 0.71, F statistic = 11.98, P = 0.002). A linear relationship was observed between aging and molecular calcification. Linear regression established that aging is a predictor of both the degree...

Macrophage antioxidant protection within atherosclerotic plaques.

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

2009-01-01

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

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

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Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min

2015-01-01

Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

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Shuang-shuang Wang

Full Text Available Formation and progression of atherosclerotic vulnerable plaque (VP is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP group (n = 10/group and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9 in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6 mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis

Atherosclerosis and the vulnerable plaque - imaging. Part II

International Nuclear Information System (INIS)

Worthley, S.G.; Helft, G.; Zaman, A.G.; Fuster, V.; Badimon, J.J.

2000-01-01

Atherosclerotic disease and its thrombotic complications remain the leading causes of mortality and morbidity in Western society. In Australia, cardiovascular disease (CVD) is responsible for one in every 2.4 (41%) deaths and is the leading single cause of mortality. The crucial final common process for the conversion of a non-occlusive, often clinically silent, atherosclerotic lesion to a potentially fatal condition is plaque disruption. The mortality associated with atherosclerotic disease relates to the acute coronary syndromes, including acute myocardial infarction (MI), unstable angina pectoris and sudden cardiac death. There is substantial clinical, experimental and post-mortem evidence demonstrating the role played by acute thrombosis upon a disrupted atherosclerotic plaque in the onset of acute coronary syndromes. Atherosclerotic plaque composition, rather than the stenotic severity, appears to be central in determining risk of both plaque rupture and subsequent thrombogenicity. In particular, a large lipid core and a thin fibrous cap render an atherosclerotic lesion susceptible or vulnerable to these complications. We are currently limited in our ability to identify accurately patients at risk for an acute coronary event. The armamentarium of diagnostic investigations, both non-invasive and invasive, currently clinically available is only able to provide us with data related to the stenotic severity of a coronary artery. The non-invasive testing includes stress-induced (exercise or pharmacologic) ischaemic changes in electrical repolarisation, wall motion or myocardial radioactive-tracer uptake. The invasive test of coronary angiography, although the current gold standard for the detection of coronary atherosclerotic disease, provides us with no data about the composition of the atherosclerotic lesion. However, the vast majority of acute coronary events involve a non-critically stenosed atherosclerotic lesion, and thus with currently available means of

Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.

Science.gov (United States)

Bobryshev, Y V; Killingsworth, M C; Lord, R S A; Grabs, A J

2008-10-01

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 microm) and presumably stable plaques, in which fibrous caps were thicker than 100 microm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908+0.544 versus 6.208+0.467 matrix vesicles per 1.92 microm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles

Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

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Shami, Annelie; Gonçalves, Isabel; Hultgårdh-Nilsson, Anna

2014-10-01

The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These novel findings will be addressed in the present review. This review covers literature focused on collagen and ECM proteins interacting with collagen, and what their roles may be in plaque development. Acute myocardial infarction and stroke are common diseases that cause disability and mortality, and the underlying mechanism is often the rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue repair in the atherosclerotic lesion are important players in plaque progression. Understanding how specific proteins in the ECM interact with cells in the plaque and affect the fate of the plaque can lead to new treatments for cardiovascular disease.

Initial stress in biomechanical models of atherosclerotic plaques

NARCIS (Netherlands)

Speelman, L.; Akyildiz, A.C.; Adel, den B.; Wentzel, J.J.; Steen, van der A.F.W.; Virmani, R.; Weerd, van der L.; Jukema, J.W.; Poelmann, R.E.; Brummelen, van E.H.; Gijsen, F.J.H.

2011-01-01

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized

Atherosclerotic plaque rupture and thrombosis. Evolving concepts.

Science.gov (United States)

Fuster, V; Stein, B; Ambrose, J A; Badimon, L; Badimon, J J; Chesebro, J H

1990-09-01

Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and

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

International Nuclear Information System (INIS)

Kang, Won Jun

2015-01-01

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

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.

Coronary Computed Tomography Angiography Derived Fractional Flow Reserve and Plaque Stress

DEFF Research Database (Denmark)

Nørgaard, Bjarne Linde; Leipsic, Jonathon; Koo, Bon-Kwon

2016-01-01

Fractional flow reserve (FFR) measured during invasive coronary angiography is an independent prognosticator in patients with coronary artery disease and the gold standard for decision making in coronary revascularization. The integration of computational fluid dynamics and quantitative anatomic...... and physiologic modeling now enables simulation of patient-specific hemodynamic parameters including blood velocity, pressure, pressure gradients, and FFR from standard acquired coronary computed tomography (CT) datasets. In this review article, we describe the potential impact on clinical practice...... and the science behind noninvasive coronary computed tomography (CT) angiography derived fractional flow reserve (FFRCT) as well as future applications of this technology in treatment planning and quantifying forces on atherosclerotic plaques....

Coronary plaque morphology on multi-modality imagining and periprocedural myocardial infarction after percutaneous coronary intervention

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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.

Cryotherapy increases features of plaque stability in atherosclerotic rabbits.

Science.gov (United States)

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

2016-08-20

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

[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs.

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Miikka Tarkia

Full Text Available Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days in farm pigs (n = 10. After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33 were harvested for ex vivo measurement of radioactivity and autoradiography (ARG.Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively. Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04. In vivo PET imaging showed the highest target-to-background ratio (TBR of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5 and either intimal thickening (1.2±0.4, P = 1.0 or atheroma (1.6±0.6, P = 0.4.We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.

Outcome of coronary plaque burden: a 10-year follow-up of aggressive medical management

OpenAIRE

Achenbach Stephan; Rumberger John A; Mohlenkamp Stefan; Lau Chu-Pak; Goh Victor K; Budoff Matthew J

2010-01-01

Abstract Background The effect of aggressive medical therapy on quantitative coronary plaque burden is not generally known, especially in ethnic Chinese. Aims We reasoned that Cardiac CT could conveniently quantify early coronary atherosclerosis in our patient population, and hypothesized that serial observation could differentiate the efficacy of aggressive medical therapy regarding progression and regression of the atherosclerotic process, as well as evaluating the additional impact of life...

Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques

Science.gov (United States)

Yu, Shann S.; Ortega, Ryan A.; Reagan, Brendan W.; McPherson, John A.; Sung, Hak-Joon; Giorgio, Todd D.

2017-01-01

An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of ‘Vulnerable atherosclerotic plaques’. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition—which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician’s toolbox—decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques. PMID:21834059

Relationship Between Endothelial Wall Shear Stress and High-Risk Atherosclerotic Plaque Characteristics for Identification of Coronary Lesions That Cause Ischemia: A Direct Comparison With Fractional Flow Reserve.

Science.gov (United States)

Han, Donghee; Starikov, Anna; Ó Hartaigh, Bríain; Gransar, Heidi; Kolli, Kranthi K; Lee, Ji Hyun; Rizvi, Asim; Baskaran, Lohendran; Schulman-Marcus, Joshua; Lin, Fay Y; Min, James K

2016-12-19

Wall shear stress (WSS) is an established predictor of coronary atherosclerosis progression. Prior studies have reported that high WSS has been associated with high-risk atherosclerotic plaque characteristics (APCs). WSS and APCs are quantifiable by coronary computed tomography angiography, but the relationship of coronary lesion ischemia-evaluated by fractional flow reserve-to WSS and APCs has not been examined. WSS measures were obtained from 100 evaluable patients who underwent coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve. Patients were categorized according to tertiles of mean WSS values defined as low, intermediate, and high. Coronary ischemia was defined as fractional flow reserve ≤0.80. Stenosis severity was determined by minimal luminal diameter. APCs were defined as positive remodeling, low attenuation plaque, and spotty calcification. The likelihood of having positive remodeling and low-attenuation plaque was greater in the high WSS group compared with the low WSS group after adjusting for minimal luminal diameter (odds ratio for positive remodeling: 2.54, 95% CI 1.12-5.77; odds ratio for low-attenuation plaque: 2.68, 95% CI 1.02-7.06; both Prelationship was observed between WSS and fractional flow reserve when adjusting for either minimal luminal diameter or APCs. WSS displayed no incremental benefit above stenosis severity and APCs for detecting lesions that caused ischemia (area under the curve for stenosis and APCs: 0.87, 95% CI 0.81-0.93; area under the curve for stenosis, APCs, and WSS: 0.88, 95% CI 0.82-0.93; P=0.30 for difference). High WSS is associated with APCs independent of stenosis severity. WSS provided no added value beyond stenosis severity and APCs for detecting lesions with significant ischemia. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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.)

Radioiodine labelled SP-4 as an imaging agent for atherosclerotic plaques

International Nuclear Information System (INIS)

Zhang Yongxue; Wu Zhijian; Cao Wei

2000-01-01

The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labelled with 131 I and 125 I by the Chloramine-T method and purified through Sephadex G-25 column. Twelve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5, NR). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then feb with high cholesterol and fat diet. 125 I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of 125 I-SP-4 in rabbits was investigated. The uptakes (% ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macro-autoradiography and micro-autoradiography were performed in 2 AR atherosclerotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. 125 I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4 hours postinjection were significantly higher than that of NR. The films of macro-autoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of micro-autoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent

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

Coronary CT Angiography in the Quantitative Assessment of Coronary Plaques

Directory of Open Access Journals (Sweden)

Zhonghua Sun

2014-01-01

Full Text Available Coronary computed tomography angiography (CCTA has been recently evaluated for its ability to assess coronary plaque characteristics, including plaque composition. Identification of the relationship between plaque composition by CCTA and patient clinical presentations may provide insight into the pathophysiology of coronary artery plaque, thus assisting identification of vulnerable plaques which are associated with the development of acute coronary syndrome. CCTA-generated 3D visualizations allow evaluation of both coronary lesions and lumen changes, which are considered to enhance the diagnostic performance of CCTA. The purpose of this review is to discuss the recent developments that have occurred in the field of CCTA with regard to its diagnostic accuracy in the quantitative assessment of coronary plaques, with a focus on the characterization of plaque components and identification of vulnerable plaques.

Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression.

Directory of Open Access Journals (Sweden)

Kevin J Woollard

Full Text Available 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.

Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques

Science.gov (United States)

Calfon, Marcella A.; Vinegoni, Claudio; Ntziachristos, Vasilis; Jaffer, Farouc A.

2010-01-01

New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics.

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

OpenAIRE

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

2013-01-01

Local hemodynamic forces, such as wall shear stress, are thought to trigger cellular and molecular mechanisms that determine atherosclerotic plaque vulnerability to rupture. Magnetic resonance imaging (MRI) has emerged as a powerful tool to characterize human carotid atherosclerotic plaque composition and morphology, and to identify plaque features shown to be key determinants of plaque vulnerability. Image-based computational fluid dynamics (CFD) has allowed researchers to obtain time-resolv...

Type D personality and coronary atherosclerotic plaque vulnerability: The potential mediating effect of health behavior.

Science.gov (United States)

Cheng, Fangman; Lin, Ping; Wang, Yini; Liu, Guojie; Li, Ling; Yu, Huai; Yu, Bo; Zhao, Zhenjuan; Gao, Xueqin

2018-05-01

The association between type D personality and coronary plaque vulnerability has been suggested. The objective of the study was to evaluate the potential mediating effects of health behavior on the association between type D personality and plaque vulnerability in coronary artery disease (CAD) patients. A total of 319 CAD patients were assessed for type D personality and health behavior via self-administered questionnaires. The plaque vulnerability, evaluated according to characteristics, accompaniment, and outcomes of plaque, was assessed by optical coherence tomography. Regression analysis showed that type D personality was independently associated with lipid plaque (odds ratio [OR] = 2.387, p = 0.001), thin cap fibroatheroma (TCFA) (OR = 2.366, p = 0.001), rupture (OR = 2.153, p = 0.002), and lipid arc (β = -0.291, p vulnerability. Psychological stress mediated the relationship between type D and lipid plaque (p = 0.030), TCFA (p = 0.034), and rupture (p = 0.013). Living habits significantly mediated the relationship between type D and lipid plaque (p = 0.028), TCFA (p = 0.036), but not rupture (p = 0.066). Participating in activities was not a significant mediator of the relationship between type D personality and lipid plaque (p = 0.115), TCFA (p = 0.115), or rupture (p = 0.077). Health behaviors (psychological stress and living habits) may be mediators of the association between type D personality and plaque vulnerability. Copyright © 2018 Elsevier Inc. All rights reserved.

Spectral CT of carotid atherosclerotic plaque: comparison with histology

Energy Technology Data Exchange (ETDEWEB)

Zainon, R.; Doesburg, R.M. [University of Canterbury, Department of Physics and Astronomy, Christchurch (New Zealand); Ronaldson, J.P.; Gieseg, S.P. [University of Otago, Centre for Bioengineering, Christchurch (New Zealand); Janmale, T. [University of Canterbury, Free Radical Biochemistry Laboratory, School of Biological Sciences, Christchurch (New Zealand); Scott, N.J. [University of Otago, Department of Medicine, Christchurch (New Zealand); Buckenham, T.M. [University of Otago, Department of Academic Radiology, Christchurch (New Zealand); Butler, A.P.H. [University of Otago, Centre for Bioengineering, Christchurch (New Zealand); University of Otago, Department of Academic Radiology, Christchurch (New Zealand); University of Canterbury, Department of Electrical and Computer Engineering, Christchurch (New Zealand); European Organisation for Nuclear Research (CERN), Geneva (Switzerland); Butler, P.H. [University of Canterbury, Department of Physics and Astronomy, Christchurch (New Zealand); European Organisation for Nuclear Research (CERN), Geneva (Switzerland); Roake, J.A. [Christchurch Hospital, Department of Vascular, Endovascular and Transplant Surgery, Christchurch (New Zealand); Anderson, N.G. [University of Otago, Centre for Bioengineering, Christchurch (New Zealand); University of Otago, Department of Academic Radiology, Christchurch (New Zealand); University of Otago, Christchurch, Department of Radiology, PO Box 4345, Christchurch (New Zealand)

2012-12-15

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

MR chemical shift imaging and spectroscopy of atherosclerotic plaque

International Nuclear Information System (INIS)

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

1989-01-01

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

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.

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

International Nuclear Information System (INIS)

Brands, P.J.M.; Poll, S.W.E. van de; Quaedackers, J.A.; Mutsaers, P.H.A.; Puppels, G.J.; Laarse, A. van der; Voigt, M.J.A. de

2001-01-01

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

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.

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

, Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg...... 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...... 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...

Characterization of HSP27 phosphorylation sites in human atherosclerotic plaque secretome

DEFF Research Database (Denmark)

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

2007-01-01

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

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

DEFF Research Database (Denmark)

Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia

2017-01-01

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...

Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study.

Science.gov (United States)

Robbins, Jeremy M; Petrone, Andrew B; Ellison, R Curtis; Hunt, Steven C; Carr, J Jeffrey; Heiss, Gerardo; Arnett, Donna K; Gaziano, J Michael; Djoussé, Luc

2014-06-01

Eggs are a ubiquitous and important source of dietary cholesterol and nutrients, yet their relationship to coronary heart disease (CHD) remains unclear. While some data have suggested a positive association between egg consumption and CHD, especially among diabetic subjects, limited data exist on the influence of egg consumption on subclinical disease. Thus, we sought to examine whether egg consumption is associated with calcified atherosclerotic plaques in the coronary arteries. In a cross-sectional design, we studied 1848 participants of the NHLBI Family Heart Study without known CHD. Egg consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age was 56.5 years and 41% were male. Median consumption of eggs was 1/week. There was no association between frequency of egg consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.95 (0.66-1.38), 0.94 (0.63-1.40), and 0.90 (0.57-1.42) for egg consumption of almost never, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.66), adjusting for age, sex, BMI, smoking, alcohol, physical activity, income, field center, total calories, and bacon. Additional control for hypertension and diabetes mellitus, or restricting the analysis to subjects with diabetes mellitus or fasting glucose >126 mg/dL did not alter the findings. These data do not provide evidence for an association between egg consumption and prevalent CAC in adult men and women.

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.)

Animal models to study plaque vulnerability

NARCIS (Netherlands)

Schapira, K.; Heeneman, S.; Daemen, M. J. A. P.

2007-01-01

The need to identify and characterize vulnerable atherosclerotic lesions in humans has lead to the development of various animal models of plaque vulnerability. In this review, current concepts of the vulnerable plaque as it leads to an acute coronary event are described, such as plaque rupture,

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.; Ellison, R. Curtis

2010-01-01

Background and Aims 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). Methods In a cross-sectional design, we studied 2,217 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. Results 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). Conclusions These data suggest that chocolate consumption might be inversely associated with prevalent CAC. PMID:20655129

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...

Localization of oxidized low-density lipoprotein and its relation to plaque morphology in human coronary artery.

Directory of Open Access Journals (Sweden)

Yasumi Uchida

Full Text Available OBJECTIVES: Oxidized low-density lipoprotein (oxLDL plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery. METHODS: Evans blue dye (EB elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM using EB as a biomarker. RESULTS: (1 By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05 higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2 By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap. CONCLUSION: Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.

Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

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Lupia, Enrico; Pucci, Angela; Peasso, Paolo; Merlo, Maurizio; Baron, Paolo; Zanini, Cristina; Del Sorbo, Lorenzo; Rizea-Savu, Simona; Silvestro, Luigi; Forni, Marco; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-09-01

Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.

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

International Nuclear Information System (INIS)

Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani; Iveson, Peter; Wilson, Ian; Karlsen, Hege; Cuthbertson, Alan; Laine, Jukka; Leppaenen, Pia; Ylae-Herttula, Seppo; Roivainen, Anne

2009-01-01

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

Is it possible to estimate cerebro–vascular risk on the basis of the composition of carotid atherosclerotic plaques?

Directory of Open Access Journals (Sweden)

Pavel Poredoš

2012-02-01

Full Text Available Different models for the prediction of cardiovascular and cerebro-vascular events are used, based on the presence of risk factors. This is a statistical risk-assessment model. Recently, research has been focused on identifying indicators that would enable us to directly assess the risk in certain individuals. These indicators include the detection of the presence and composition of atherosclerotic plaques. Atherosclerotic plaques found in a majority of adults represent a potential cause of vascular complications. Recently, not only thestage of atherosclerotic plaques or the degree of arterial stenosis but also the knowledge of atherosclerotic plaque composition is gaining in importance. Particularly unstable plaques, which are prone to disintegration and the associatedthromboembolic complications, are considered dangerous. Therefore, recently intensive research has been underway to find methods that would enable us to identify the composition and in particular the biological activity of atherosclerotic plaques. Namely, the latter two features determine the stability of plaques or their proneness to rupture and disintegration. While classical angiography is invasive and associated with irradiation, it only provides information on the degree of vascular lumen stenosis but not also on vascular wall composition. Ultrasonography is a basic non-invasive imaging method, which also provides an insight into the composition of vascular wall, however, since mainly superficially situated arteries are accessible by US, its investigation potential in distinguishing between different tissue structures is rather limited. Recent computer programs for analysis of ultrasound images and quantifying various components of atherosclerotic plaques provide a more accurate determination of the composition of atherosclerotic plaques, but do not yield information on the biological activity of atherosclerotic lesions.A newer generation of imaging methods facilitates more

Comparison of traditional cardiovascular risk models and coronary atherosclerotic plaque as detected by computed tomography for prediction of acute coronary syndrome in patients with acute chest pain.

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Ferencik, Maros; Schlett, Christopher L; Bamberg, Fabian; Truong, Quynh A; Nichols, John H; Pena, Antonio J; Shapiro, Michael D; Rogers, Ian S; Seneviratne, Sujith; Parry, Blair Alden; Cury, Ricardo C; Brady, Thomas J; Brown, David F; Nagurney, John T; Hoffmann, Udo

2012-08-01

The objective was to determine the association of four clinical risk scores and coronary plaque burden as detected by computed tomography (CT) with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain. The hypothesis was that the combination of risk scores and plaque burden improved the discriminatory capacity for the diagnosis of ACS. The study was a subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial-a prospective observational cohort study. The authors enrolled patients presenting to the emergency department (ED) with a chief complaint of acute chest pain, inconclusive initial evaluation (negative biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers, and subsequent diagnostic testing, such as exercise treadmill testing, nuclear stress perfusion imaging, and/or invasive coronary angiography), as deemed clinically appropriate. The clinical providers were blinded to CT results. The chest pain score was calculated and the results were dichotomized to ≥10 (high-risk) and modeling was performed to examine the association of risk scores and coronary plaque burden to the outcome of ACS. Unadjusted models were individually fitted for the coronary plaque burden and for Goldman, Sanchis, TIMI, and chest pain scores. In adjusted analyses, the authors tested whether the association between risk scores and ACS persisted after controlling for the coronary plaque burden. The prognostic discriminatory capacity of the risk scores and plaque burden for ACS was assessed using c-statistics. The differences in area under the receiver-operating characteristic curve (AUC) and c-statistics were tested by performing the -2 log likelihood ratio test of nested models. A p value capacity for the diagnosis of ACS. Plaque burden was

Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography

International Nuclear Information System (INIS)

Cademartiri, Filippo; Krestin, Gabriel P.; Mollet, Nico R.; Feyter, Pim J. de; Runza, Giuseppe; Midiri, Massimo; Bruining, Nico; Hamers, Ronald; Somers, Pamela; Knaapen, Michiel; Verheye, Stefan

2005-01-01

Assessment of attenuation (measured in Hounsfield units, HU) of human coronary plaques was performed using multislice computed tomography (MSCT) in an ex vivo model. In three ex vivo specimens of left coronary arteries in oil, MSCT was performed after intracoronary injection of four solutions of contrast material (400 mgI/ml iomeprol). The four solutions were diluted as follows: 1/∞, 1/200, 1/80, and 1/20. All scans were performed with the following parameters: slices/collimation 16/0.75 mm, rotation time 375 ms. Each specimen was scored for the presence of atherosclerotic plaques. In each plaque the attenuation was measured in four regions of interest for lumen, plaque (non-calcified thickening of the vessel wall), calcium, and surrounding (oil surrounding the vessel). The results were compared with a one-way analysis of variance test and were correlated with Pearson's test. There were no significant differences in the attenuation of calcium and oil in the four solutions. The mean attenuation in the four solutions for lumen (35±10, 91±7, 246±18, 511±89 HU) and plaque (22±22, 50±26, 107±36, 152±67 HU) was significantly different between each decreasing dilution (p<0.001). The mean attenuation of lumen and plaque of coronary plaques showed high correlation, while the values were significantly different (r=0.73; p<0.001). Intracoronary attenuation modifies significantly the attenuation of plaques assessed with MSCT. (orig.)

Optical Coherence Tomography Imaging in Acute Coronary Syndromes

Directory of Open Access Journals (Sweden)

Takashi Kubo

2011-01-01

Full Text Available Optical coherence tomography (OCT is a high-resolution imaging technique that offers microscopic visualization of coronary plaques. The clear and detailed images of OCT generate an intense interest in adopting this technique for both clinical and research purposes. Recent studies have shown that OCT is useful for the assessment of coronary atherosclerotic plaques, in particular the assessment of plaque rupture, erosion, and intracoronary thrombus in patients with acute coronary syndrome. In addition, OCT may enable identifying thin-cap fibroatheroma, the proliferation of vasa vasorum, and the distribution of macrophages surrounding vulnerable plaques. With its ability to view atherosclerotic lesions in vivo with such high resolution, OCT provides cardiologists with the tool they need to better understand the thrombosis-prone vulnerable plaques and acute coronary syndromes. This paper reviews the possibility of OCT for identification of vulnerable plaques in vivo.

Assessment of coronary artery disease and calcified coronary plaque burden by computed tomography in patients with and without diabetes mellitus

Energy Technology Data Exchange (ETDEWEB)

Maffei, Erica; Seitun, Sara [Azienda Ospedaliero-Universitaria di Parma, Department of Radiology and Cardiology, Parma (Italy); Nieman, Koen; Weustink, Annick C.; Mollet, Nico R. [Erasmus Medical Center, Department of Radiology and Cardiology, Rotterdam (Netherlands); Martini, Chiara [Azienda Ospedaliero-Universitaria di Parma, Department of Radiology and Cardiology, Parma (Italy); Erasmus Medical Center, Department of Radiology and Cardiology, Rotterdam (Netherlands); Guaricci, Andrea Igoren [Azienda Ospedaliero-Universitaria di Foggia, Department of Cardiology, Foggia (Italy); Tedeschi, Carlo [Ospedale San Gennaro, Department of Cardiology, Naples (Italy); Berti, Elena; Grilli, Roberto [Regione Emilia-Romagna, Healthcare and Social Agency, Bologna (Italy); Messalli, Giancarlo [SDN Foundation, IRCCS, Naples (Italy); Cademartiri, Filippo [Azienda Ospedaliero-Universitaria di Parma, Department of Radiology and Cardiology, Parma (Italy); Erasmus Medical Center, Department of Radiology and Cardiology, Rotterdam (Netherlands); Azienda Ospedaliero-Universitaria - Parma, Department of Radiology, Parma (Italy)

2011-05-15

To compare the coronary atherosclerotic burden in patients with and without type-2 diabetes using CT Coronary Angiography (CTCA). 147 diabetic (mean age: 65 {+-} 10 years; male: 89) and 979 nondiabetic patients (mean age: 61 {+-} 13 years; male: 567) without a history of coronary artery disease (CAD) underwent CTCA. The per-patient number of diseased coronary segments was determined and each diseased segment was classified as showing obstructive lesion (luminal narrowing >50%) or not. Coronary calcium scoring (CCS) was assessed too. Diabetics showed a higher number of diseased segments (4.1 {+-} 4.2 vs. 2.1 {+-} 3.0; p < 0.0001); a higher rate of CCS > 400 (p < 0.001), obstructive CAD (37% vs. 18% of patients; p < 0.0001), and fewer normal coronary arteries (20% vs. 42%; p < 0.0001), as compared to nondiabetics. The percentage of patients with obstructive CAD paralleled increasing CCS in both groups. Diabetics with CCS {<=} 10 had a higher prevalence of coronary plaque (39.6% vs. 24.5%, p = 0.003) and obstructive CAD (12.5% vs. 3.8%, p = 0.01). Among patients with CCS {<=} 10 all diabetics with obstructive CAD had a zero CCS and one patient was asymptomatic. Diabetes was associated with higher coronary plaque burden. The present study demonstrates that the absence of coronary calcification does not exclude obstructive CAD especially in diabetics. (orig.)

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

NARCIS (Netherlands)

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

2013-01-01

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

Association of CD147 genetic polymorphisms with carotid atherosclerotic plaques in a Han Chinese population with cerebral infarction.

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Ni, Tongtian; Chen, Min; Yang, Kang; Shao, Jianwei; Fu, Yi; Zhou, Weijun

2017-08-01

Given the important role of CD147 in the development of atherosclerosis, we speculated that CD147 genetic polymorphisms might influence the formation of carotid atherosclerotic plaques. The study was to investigate the association between CD147 gene polymorphisms and susceptibility to carotid atherosclerotic plaques in individuals with cerebral infarction (CI). Eight SNPs in the regulatory and coding regions of the CD147 gene were examined using polymerase chain reaction-ligase detection reaction (PCR-LDR) in DNA samples from 732 Chinese patients with CI, divided into a carotid plaque group (n=475) and a non-carotid plaque group (n=257). Significant differences were found in the genotypes and allele frequencies of the rs4919862 SNP between the carotid plaque and non-carotid plaque groups of CI patients (PCD147 was closely associated with carotid atherosclerotic plaques formation. Thus, polymorphisms of the CD147 gene may be related to the tendency for carotid atherosclerotic plaques. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

2013-01-01

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

{sup 68}Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

Energy Technology Data Exchange (ETDEWEB)

Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Iveson, Peter; Wilson, Ian [Medical Diagnostics, GE Healthcare Biosciences, London (United Kingdom); Karlsen, Hege; Cuthbertson, Alan [GE Healthcare MDx Research, Oslo (Norway); Laine, Jukka [Turku University Hospital, Department of Pathology, Turku (Finland); Leppaenen, Pia; Ylae-Herttula, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland); Roivainen, Anne [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Turku Centre for Disease Modelling, Turku (Finland)

2009-12-15

Increased expression of {alpha}v{beta}3/{alpha}v{beta}5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel {sup 68}Ga-DOTA-RGD peptide binds with high affinity to {alpha}v{beta}3/{alpha}v{beta}5 integrin. The aim of this study was to investigate the uptake of the {sup 68}Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered {sup 68}Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR{sup -/-}ApoB{sup 100/100} atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced {sup 68}Ga. The tracer had reasonably good specific radioactivity (8.7 {+-} 1.1 GBq/{mu}mol) and was quite stable in vivo. According to ex vivo biodistribution results, {sup 68}Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of {sup 68}Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio {+-} SD 1.4 {+-} 0.1, p = 0.0004). We observed that {sup 68}Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

Experimental study of 99Tcm-Ap4A in detection of atherosclerotic plaques

International Nuclear Information System (INIS)

Cao Wei; Zhang Yongxue; An Rui

2001-01-01

Objective: To study 99 Tc m labelled di-adenosine tetraphosphate (Ap4A), a compound can bind on P 2 purine receptors on atherosclerotic lesions, for imaging experimental atherosclerotic plaques in New Zealand White (NZW) rabbits. Methods: Twenty male NZW rabbits were submitted immune-injury and fed with high cholesterol diet for more than 2 months. To label the 99 Tc m to Ap4A, stannous tartrate solution was used. 99 Tc m -Ap4A was purified on a Sephadex G-25 column and tested for radiochemistry purity on thin layer chromatography. A biodistribution study was carried out on KM mice. Thirty minutes after intravenous injection of 7.4 MBq 99 Tc m -Ap4A, 5 normal NZW rabbits and 5 NZW rabbits with atherosclerotic lesions were sacrificed; their abdominal aortas were removed and covered with X-ray films. Exposed for 24 h in refrigerator, the films were developed and fixed. In another 5 NZW rabbits with atherosclerotic lesions, blood samples, atherosclerotic plaques and normal aortic wall samples were removed. Lesion to blood (target/blood, T/B), lesion to normal (target/non-target, T/NT) radioactivity ratios were calculated. 74 MBq 99 Tc m -Ap4A was injected into marginal ear veins of 5 atherosclerotic and 5 normal NZW rabbits. Simultaneously in vivo images were recorded for more than 4 h. In another group, 30 min after 99 Tc m -Ap4A administration, the animals were sacrificed and their abdominal aortas were removed. The abdominal aortas were placed on the face of SPECT and images acquisition was performed. Results: The radiochemistry purity of 99 Tc m -Ap4A was 85% to 91%. Biodistribution study revealed the clearance of 99 Tc m -Ap4A from blood was rapid. Thirty min after 99 Tc m -Ap4A administration, T/B radio was 3.17 +- 1.27, T/NT ratio was 5.23 +- 1.87. On the radioautography film shadows of atherosclerotic plaques were clearly visible. The atherosclerotic plaques on the aorta samples also can be seen on ex vivo images. Atherosclerotic abdominal aortas and lesions

[Association of human epicardial adipose tissue volume and inflammatory mediators with atherosclerosis and vulnerable coronary atherosclerotic plaque].

Science.gov (United States)

Zhou, Liangliang; Gong, Jianbin; Li, Demin; Lu, Guangming; Chen, Dong; Wang, Jing

2015-02-01

To investigate the relation of epicardial adipose tissue volume (EATV) determined by dual-source CT (DSCT) cardiac angiography and EAT-derived inflammatory factors to coronary heart disease (CHD) and vulnerable plaque. A total of 260 patients underwent cardiac computed tomography to evaluate stenosis of coronary artery, and blood samples were obtained from each patient. CHD was confirmed in 180 patients by DSA and CHD was excluded in the remaining 80 patients (NCHD). Vascular remodeling index and plaque vulnerability parameters (fatty volume, fibrous volume and calcification volume and fiber volume) were measured in CHD patients and correlation with EATV was analyzed. Epicardial adipose tissue (EAT) and intrathoracic adipose tissue (TAT) were collected from 40 CHD patients undergoing CABG surgery, and, mRNA and protein expressions of leptin and MMP9 were detected by RT-PCR and Western blot analysis. (1) The EATV was significantly higher in the CHD group than in NCHD group ((121.2 ± 40.6) mm³ vs. (74.7 ± 18.1) mm³, P = 0.01). (2) Subgroup analysis of the CHD patients demonstrated that EATV was significantly higher in patients with positive remodeling than in patients without positive remodeling ((97.6 ± 42.0) cm³ vs. (75.5 ± 25.4) cm³, P = 0.01). Lipid plaque volume was positively correlated with EATV (r = 0.34, P = 0.002); however, fiber plaque volume was negatively correlated with EATV (r = -0.30, P = 0.008). (3) Logistic regression analysis indicated that EATV was an independent risk factor for positive vascular remodeling (OR = 2.01, 95% CI: 1.30-2.32, P = 0.01). (4) mRNA and protein expression of leptin and MMP9 in EAT was significantly upregulated in 40 CHD patients who received CABG surgery compared to 40 NCHD patients (P 0.05) in mRNA and protein expression of leptin and MMP9 from the SAT between CHD and NCHD patients. (5) In the CHD group, leptin and MMP9 levels in EAT and EATV were positively correlated with lipid plaque volume and fibrous plaque

Bone marrow endothelial progenitors in atherosclerotic plaque resolution

Science.gov (United States)

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

2013-01-01

Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

Calcified Plaque of Coronary Artery: Factors Influencing Overestimation of Coronary Artery Stenosis on Coronary CT Angiography

International Nuclear Information System (INIS)

Kim, Mok Hee; Kim, Yun Hyeon; Choi, Song; Seon, Hyun Ju; Jeong, Gwang Woo; Park, Jin Gyoon; Kang, Heoung Keun; Ko, Joon Seok

2010-01-01

To assess the influence of calcified plaque characteristics on the overestimation of coronary arterial stenosis on a coronary CT angiography (CCTA). The study included 271 coronary arteries with calcified plaques identified by CCTA, and based on 928 coronary arteries from 232 patients who underwent both CCTA and invasive coronary angiography (ICA). Individual coronary arteries were classified into two groups by agreement based on the degree of stenosis from each CCTA and ICA: 1) group A includes patients with concordant CCTA and ICA results and, 2) group B includes patients with an overestimation of CCTA compared to ICA. Parameters including total calcium score, calcium score of an individual coronary artery, calcium burden number of an individual coronary artery, and the density of each calcified plaque (calcium score / number of calcium burden) for each individual coronary artery were compared between the two groups. Of the 271 coronary arteries, 164 (60.5%) were overestimated on CCTA. The left anterior descending artery (LAD) had a significantly low rate of overestimation (47.1%) compared to the other coronary arteries (p=0.001). No significant differences for total calcium score, calcium score of individual coronary artery, and the density of each calcified plaque from individual coronary arteries between two groups was observed. However, a decreasing tendency for the rate of overestimation on CCTA was observed with an increase in calcium burden of individual coronary arteries (p<0.05). The evaluation of coronary arteries suggests that the degree of coronary arterial stenosis had a tendency to be overestimated by calcified plaques on CCTA. However, the rate of overestimation for the degree of coronary arterial stenosis by calcified plaques was not significantly influenced by total calcium score, calcium score of individual coronary artery, and density of each calcified plaque

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

NARCIS (Netherlands)

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

2015-01-01

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

HDL mimetic CER-001 targets atherosclerotic plaques in patients.

Science.gov (United States)

Zheng, Kang He; van der Valk, Fleur M; Smits, Loek P; Sandberg, Mara; Dasseux, Jean-Louis; Baron, Rudi; Barbaras, Ronald; Keyserling, Constance; Coolen, Bram F; Nederveen, Aart J; Verberne, Hein J; Nell, Thijs E; Vugts, Danielle J; Duivenvoorden, Raphaël; Fayad, Zahi A; Mulder, Willem J M; van Dongen, Guus A M S; Stroes, Erik S G

2016-08-01

Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co-administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. Netherlands Trial Registry - NTR5178. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5178. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

Science.gov (United States)

Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

2015-09-01

Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

Experimental study of multi-slice CT for the evaluation of atherosclerotic plaques

International Nuclear Information System (INIS)

Tang Xiang; Lv Bin; Wu Wenhui; Lu Jinguo; Dai Ruping; Bai Hua; Tang Yue; Lv Fengying; Jiang Shiliang

2009-01-01

Objective: To evaluate the diagnostic values of MSCT for detecting atherosclerotic plaques on New Zealand rabbits models in comparison with pathologic results. Methods: Fifteen New Zealand rabbits were enrolled in this study, including 5 with balloon injury and high-fat diet (group A), 5 with high-fat diet only (group B) and 5 with regular feed (group C). 16th week late, contrast-enhanced MSCT scan was performed in all rabbits with 16 slice MSCT (16-MSCT) in group A and 64 slice MSCT (64-MSCT) in group B and C. The CT and pathological findings were compared in a double-blind manner. The sensitivities and specificities of 16-MSCT and 64-MSCT for detecting atherosclerotic plaques were evaluated by using Fisher test and χ 2 test. Results: Sixty and seventy-five images on 16-MSCT and 64-MSCT had corresponding pathological slices. The sensitivities for the detection of plaques on 16-MSCT and 64-MSCT were 41.5% (22/53) and 64.9% (24/37), and specificities of 85.7% (6/7) and 89.5% (34/38), respectively. Conclusions: 64-MSCT has a higher sensitivity in the detection of atherosclerotic plaques than 16-MSCT. Both scanners can be used to preclude the diagnosis of atherosclerosis. (authors)

Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes

NARCIS (Netherlands)

Briley-Saebo, Karen C.; Mulder, Willem J. M.; Mani, Venkatesh; Hyafil, Fabien; Amirbekian, Vardan; Aguinaldo, Juan Gilberto S.; Fisher, Edward A.; Fayad, Zahi A.

2007-01-01

The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of

The impact of splenectomy on human coronary artery atherosclerosis and vascular macrophage distribution.

Science.gov (United States)

Li, Yu; Stone, James R

Splenectomy can potentially impact atherosclerosis through multiple mechanisms including altered lipid homeostasis, increased coagulation, and altered macrophage recruitment to the plaque. In patients, splenectomy has been associated with increased rates of coronary artery events, while in experimental mice, splenectomy causes increased atherosclerosis but reduces systemic monocyte supply. In this study, the direct impact of splenectomy on human coronary artery atherosclerotic plaque severity and macrophage content was investigated. Coronary artery atherosclerotic plaque severity was determined at autopsy in 18 long-term (≥10 years) splenectomy patients and 90 matched control patients. Coronary artery macrophage content was evaluated in mild atherosclerotic plaques of 11 mid- to long-term (≥1 year) splenectomy patients and 11 matched control patients. Splenectomy was associated with reduced coronary artery atherosclerosis (P=.03). The association was most pronounced for the subgroup of patients who had undergone splenectomy 20 years or more prior to death (P=.02). There was no difference in the density of macrophages in the plaque, media, or adventitia upon comparing splenectomy and control patients. In the control group, there was no correlation between the macrophage densities in the three arterial layers. However, in the splenectomy patients, there was a strong correlation in the macrophage densities across the plaque, media, and adventitia (P≤.0002), with resulting slopes that were significantly greater than seen in the control patients (P=.0007-.011). These findings indicate that, in humans, splenectomy is associated with lower coronary artery atherosclerotic plaque severity and altered coronary artery macrophage distribution. These results suggest that the spleen can modulate the recruitment of macrophages into human coronary arteries and the progression of atherosclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of atherosclerotic plaque activity and vascular inflammation using [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

Science.gov (United States)

Mehta, Nehal N; Torigian, Drew A; Gelfand, Joel M; Saboury, Babak; Alavi, Abass

2012-05-02

Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide information about the burden of disease. However, despite multiple validation studies of CAC, and C-IMT, these modalities do not accurately assess plaque characteristics, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events. [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an important source of cellular inflammation in vessel walls. More recently, we and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy as well as longer term therapeutic lifestyle changes (16 months). The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is

Gender differences in coronary plaque composition by coronary computed tomography angiography.

Science.gov (United States)

Blaha, Michael J; Nasir, Khurram; Rivera, Juan J; Choi, Eue-Keun; Chang, Sung-A; Yoon, Yeonyee E; Chun, Eun Ju; Choi, Sang-il; Agatston, Arthur; Blumenthal, Roger S; Chang, Hyuk-Jae

2009-12-01

Coronary computed tomography angiography allows the differentiation of non-calcified (NCAP), calcified (CAP), and mixed coronary artery plaques (MCAP). Although males are thought to have a higher prevalence of atherosclerosis for a given age, there are currently few data regarding age-adjusted sex differences in plaque morphology and composition. We studied 1015 consecutive asymptomatic South Korean patients (49+/-10 years, 64% men) who underwent 64-slice coronary computed tomography angiography during a routine health evaluation. Coronary plaque characteristics were analyzed on a per-segment basis according to the modified AHA classification. Plaques with more than 50% calcified tissue were classified as CAP, plaques with less than 50% calcified tissue were classified as MCAP, and plaques without calcium were classified as NCAP. Multiple regression analysis was used to describe the cross-sectional association between sex and plaque-type burden (>or=2 affected segments) after adjustment for age and other cardiovascular risk factors. There was a greater prevalence of coronary plaque among men (13 vs. 4%, PNCAP was similar across sex (2 vs. 1%, P = 0.28). After multivariable adjustment, men have six to seven times greater odds of having an increased burden of CAP and MCAP, whereas no sex difference was observed in the burden of NCAP. In this population of asymptomatic middle-aged Korean individuals, males had a significantly greater burden of MCAP and CAP. Future studies will determine whether these differences contribute to the accelerated cardiovascular risk observed in men.

Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

Science.gov (United States)

Guo, Muyi; Cai, Yan; Yao, Xinke; Li, Zhiyong

2018-08-07

Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum. Three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemicals (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase) are involved in the plaque progression model, and described by the reaction-diffusion partial differential equations. The hemodynamic calculation of the microcirculation on the generated microvessel network is carried out by coupling the intravascular, interstitial and transvascular flow. The plasma concentration in the interstitial domain is defined as the description of IPH area according to the diffusion and convection with the interstitial fluid flow, as well as the extravascular movement across the leaky vessel wall. The simulation results demonstrate a series of pathophysiological phenomena during the vulnerable progression of an atherosclerotic plaque, including the expanding necrotic core, the exacerbated inflammation, the high microvessel density (MVD) region at the shoulder areas, the transvascular flow through the capillary wall and the IPH. The important role of IPH in the plaque destabilization is evidenced by simulations with varied model parameters. It is found that the IPH can significantly speed up the plaque vulnerability by increasing necrotic core and thinning fibrous cap. In addition, the decreased MVD and vessel permeability may slow down the process of

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.

The formation of atherosclerotic plaque, its destabilisation and diagnostics

Directory of Open Access Journals (Sweden)

Piotr Kaźmierski

2014-04-01

Full Text Available According to the established medical knowledge, the atheromatous lesions occur in the arteries of large and medium diameter. Their presence in the aorta, arteries of extremities as well as extracerebral and coronal arteries is clinically relevant. The evolution of atherosclerotic plaques probably starts in the prenatal development, what may be proved by the presence of the fatty streaks in endothelium of coronal arteries in some newborns. Then it evolves through lipid accumulation, media inflammatory response, vasa vasorum proliferation, fibrination and calcification of plaques. Researches proved that the matter of atherosclerosis is exaggerated inflammatory proliferative reaction to the arterial wall damage. The oxidative stress phenomenon and infections with common pathogens play an undoubtful role in this process. Ultimately the direct damage is an effect of immune response cells infiltration and secretion of cytokines and proinflammatory factors. Among the cells of immune system responsible for formation and development of atheromatous plaque are considered: macrophages, dendritic cells, T and B lymphocytes, monocytes. Attention was also paid to the inflammatory mediators and growth factors. Scientist are interested in unstable atherosclerotic plaque and accompanying inflammatory process within the artery wall for a long time. Meanwhile, there are conducted researches on inflammation markers underlying the destabilisation of plaques. Revealing the role of these cells in evolution of atherosclerosis would enable more complex understanding of the mechanism of lesions development. Then it would facilitate an introduction of the new and upgraded methods of treatment and prevention. Also the progress of imaging examinations is meaningful for diagnostics and treatment. It is contributory to the choice of therapeutic strategy and assessment of surgical intervention urgency. In the clinical practice there are recognized standards of imaging the

Coronary plaque quantification and fractional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions

DEFF Research Database (Denmark)

Gaur, Sara; Øvrehus, Kristian Altern; Dey, Damini

2016-01-01

AIMS: Coronary plaque characteristics are associated with ischaemia. Differences in plaque volumes and composition may explain the discordance between coronary stenosis severity and ischaemia. We evaluated the association between coronary stenosis severity, plaque characteristics, coronary computed...... tomography angiography (CTA)-derived fractional flow reserve (FFRCT), and lesion-specific ischaemia identified by FFR in a substudy of the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). METHODS AND RESULTS: Coronary CTA stenosis, plaque volumes, FFRCT, and FFR were assessed...

Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

Science.gov (United States)

Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

2012-11-01

To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both Padvanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, Padvanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, Padvanced coronary plaques. © RSNA, 2012

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

Directory of Open Access Journals (Sweden)

Elisabetta Zinellu

2012-01-01

Full Text Available Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS. The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P<0.01 in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability.

Physical model of the haemodynamic effects around the obstructing plaque in the acute coronary syndromes take account of the stenosis geometry

International Nuclear Information System (INIS)

Matveev, M.

2004-01-01

Selective coronary angiography with quantitative parameter assessment of the vessel stenosis geometry, which leads to acute coronary syndrome, was performed in 205 patients undergoing acute phase of myocardial infarction or unstable angina pectoris. Data for physicomechanical properties of the arterial vessels, blood and blood flow were used. The range of pressure variations accompanying the most frequently encountered ruptures of the atherosclerotic plaques was analyzed with physical model. It suggests that in 'lock' type plaques the ratio between the pressure on the wall of the normal vessel and that in the section outside the stenosis is considerably increased, especially in cases of enlarged vessel gauge. The results obtained show that the wall pressure closely to the plaque of a stenosed vessel with normal diameter of 3.5 mm exceeds 25 times the pressure within a normal vessel segment. (author)

Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography.

Science.gov (United States)

Utsunomiya, Hiroto; Yamamoto, Hideya; Kunita, Eiji; Kitagawa, Toshiro; Ohashi, Norihiko; Oka, Toshiharu; Yamazato, Ryo; Horiguchi, Jun; Kihara, Yasuki

2010-11-01

We examined the association of aortic valve calcification (AVC) and mitral annular calcification (MAC) to coronary atherosclerosis using 64-multidetector computed tomography (MDCT). Valvular calcification is considered a manifestation of atherosclerosis. The impact of multiple heart valve calcium deposits on the distribution and characteristics of coronary plaque is unknown. We evaluated 322 patients referred for 64-MDCT, and assessed valvular calcification and the extent of calcified (CAP), mixed (MCAP), and noncalcified coronary atherosclerotic plaque (NCAP) in accordance with the 17-coronary segments model. We assessed the vulnerable characteristics of coronary plaque with positive remodeling, low-density plaque (CT density ≤38 Hounsfield units), and the presence of adjacent spotty calcification. In 49 patients with both AVC and MAC, the segment numbers of CAP and MCAP were larger than in those with a lack of valvular calcification and an isolated AVC (pNCAP. Moreover, it was also related to the presence of coronary plaque with all three vulnerable characteristics (OR 4.87, 95%CI 1.85-12.83, p=0.001). The combined presence of AVC and MAC is highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-MDCT. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The complex fate in plasma of gadolinium incorporated into high-density lipoproteins used for magnetic imaging of atherosclerotic plaques

NARCIS (Netherlands)

Barazza, Alessandra; Blachford, Courtney; Even-Or, Orli; Joaquin, Victor A.; Briley-Saebo, Karen C.; Chen, Wei; Jiang, Xian-Cheng; Mulder, Willem J. M.; Cormode, David P.; Fayad, Zahi A.; Fisher, Edward A.

2013-01-01

We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL,

CT virtual intravascular endoscopy assessment of coronary artery plaques: A preliminary study

International Nuclear Information System (INIS)

Sun Zhonghua; Dimpudus, Franky Jacobus; Nugroho, Johanes; Adipranoto, Jeffrey Daniel

2010-01-01

Purpose: The purpose of this study was to investigate the potential value of CT virtual intravascular endoscopy (VIE) in the visualization and assessment of coronary plaques in patients suspected of coronary artery disease. Materials and methods: 20 (13 men, 7 women, mean age 54 years) consecutive patients with suspected coronary artery disease undergoing 64-slice CT angiography were included in the study. Four main coronary artery branches were assessed with regard to the presence of coronary plaques based on 2D axial, multiplanar reformation, 3D volume rendering and VIE visualizations. The coronary plaques were characterized into calcified, noncalcified and mixed plaques. The intraluminal appearances of these coronary plaques were demonstrated with VIE images and correlated with 2D and 3D images to determine the diagnostic value of VIE for the assessment of the plaques. Results: VIE was able to identify and demonstrate the intraluminal appearances of coronary plaques in 18 patients involving 32 coronary artery branches which were shown as an irregularly intraluminal protruding sign in extensively calcified plaques and smooth protruding appearance in noncalcified or focally calcified plaques. An irregular intraluminal appearance was also noticed in the presence of mixed plaques due to variable components with different CT attenuations contained within the plaques. VIE accurately confirmed the degree of coronary stenosis or occlusion despite the presence of heavy calcification. Conclusion: VIE could be used as a complementary tool to conventional CT visualizations for the analysis of luminal changes and assessment of disease extent caused by the coronary plaques.

Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

NARCIS (Netherlands)

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

2012-01-01

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

Mechanical properties of human atherosclerotic intima tissue.

Science.gov (United States)

Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

2014-03-03

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

A comparison of directional atherectomy with coronary angioplasty in patients with coronary artery disease

NARCIS (Netherlands)

E.J. Topol (Eric); F. Leya; C.A. Pinkerton; P.L. Whitlow (Patrick); B. Hofling; C.A. Simonton; R.R. Masden; P.W.J.C. Serruys (Patrick); M.B. Leon (Martin); D.O. Williams (David); S.B. King 3rd (Spencer); B. Daniel; D.B. Mark (Daniel); J.M. Isner; D.R. Holmes Jr (David); S.G. Ellis (Stephen); K.L. Lee (Kerry); G.P. Keeler; L.G. Berdan (Lisa); T. Hinohara; R.M. Califf (Robert)

1993-01-01

textabstractBACKGROUND. Directional coronary atherectomy is a new technique of coronary revascularization by which atherosclerotic plaque is excised and retrieved from target lesions. With respect to the rate of restenosis and clinical outcomes, it is not known how this procedure compares with

Intravascular Photoacoustic Imaging : A New Tool for Vulnerable Plaque Identification

NARCIS (Netherlands)

Jansen, K.; Van Soest, G.; Van der Steen, A.F.W.

2014-01-01

The vulnerable atherosclerotic plaque is believed to be at the root of the majority of acute coronary events. Even though the exact origins of plaque vulnerability remain elusive, the thin-cap fibroatheroma, characterized by a lipid-rich necrotic core covered by a thin fibrous cap, is considered to

Dynamic contrast-enhanced MRI examination of atherosclerotic plaques: an animal study using rabbit model

International Nuclear Information System (INIS)

Li Mingli; Sun Jie; Chang Xiaoyan; Jin Zhengyu

2011-01-01

Objective: The enhanced patterns of atherosclerotic plaque on dynamic contrast- enhanced MRI have not been well studied. The aim of this study was to explore the patterns of plaque enhancement and their underlying mechanism by using dynamic contrast-enhanced MRI (DCE-MRI). Methods: Atherosclerotic plaques were induced in the aorta of 12 New Zealand White rabbits by a combination of endothelial denudation and high-cholesterol diet. Ten to sixteen weeks after surgery, DCE- MRI was performed with a fast spin echo T 1 weighted sequence. Thirty-five phases of images were obtained at 71-second intervals. Gd-DTPA was injected coincident with the third scan via marginal ear vein. Specimens were harvested within 12 hours after imaging for HE staining and CD31 immunohistochemical staining which was used to highlight neo-vessels. Plaque enhancement patterns were studied and compared with histological findings. Signal intensity of each plaque section was normalized to pre-contrast signal intensity of psoas muscle, after which signal intensity versus time curve was drawn. Pearson correlation coefficient was used to reveal association between histological neo-vessel count and descriptive parameters derived from signal intensity versus time curve. Results: Plaques were significantly enhanced by Gd-DTPA. Enhancement patterns could be described as 'fast-in and slow-out'. Differences in patterns of enhancement were observed between tissues, with fibrous tissue enhanced more than lipid aggregation and leukocyte foci. Peak enhancement (1.05±0.30), initial slope (0.82±0.28) and area under the curve at early phase (4.97± 1.67) derived from signal intensity-time curve had significant correlations with neo-vessel count (117.7± 93.3) (r=0.553, 0.468, 0.554 respectively, P<0.05). Conclusions: The enhanced patterns of atherosclerotic plaque by Gd-DTPA were 'fast- in and slow-out'. Neovascularization, increased endothelial permeability and extracellular matrix may be the reasons for

Morphological differences in coronary arteries following rotational atherectomy versus balloon angioplasty: ultrasound and angioscopic observations

Science.gov (United States)

Bass, Theodore A.; Gilmore, Paul S.; White, Christopher J.; Chami, Youssef G.; Kircher, Barbara J.; Conetta, Donald A.

1993-09-01

Percutaneous transluminal coronary rotational atherectomy (PTCRA) is an exciting new device to recannulate obstructed coronary arteries. This device works as a high speed `drill,' selectively cutting hard atherosclerotic plaque while preferentially sparing the softer, less diseased vascular luminal surface. At speeds as high as 200,000 rpm the plaque is pulverized into small particles easily handled by the circulatory system with no untoward clinical sequela. Balloon angioplasty does not remove atherosclerotic plaque. It dilates the vessel by mechanically stretching, compressing and splitting the plaque and vessel lining. We compare morphological and surface luminal characteristics of vessels post PTCRA to vessels post PTCA.

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

International Nuclear Information System (INIS)

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

2005-01-01

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

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

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease.

Science.gov (United States)

Pasterkamp, Gerard; den Ruijter, Hester M; Libby, Peter

2017-01-01

The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

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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.

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

NARCIS (Netherlands)

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

2014-01-01

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

Multiple yellow plaques assessed by angioscopy with quantitative colorimetry in patients with myocardial infarction.

Science.gov (United States)

Inami, Shigenobu; Ishibashi, Fumiyuki; Waxman, Sergio; Okamatsu, Kentaro; Seimiya, Koji; Takano, Masamichi; Uemura, Ryota; Sano, Junko; Mizuno, Kyoichi

2008-03-01

Multiple angioscopic yellow plaques are associated with diffuse atherosclerotic plaque, and may be prevalent in patients with myocardial infarction (MI), so in the present study the yellow plaques in the coronary arteries of patients with MI was evaluated using quantitative colorimetry, and compared with those of patients with stable angina (SA). In the recorded angioscopic images of 3 coronary vessels in 29 patients (15 patients with MI, 14 with SA), yellow plaques were determined as visually yellow regions with b* value >0 (yellow color intensity) measured by the quantitative colorimetric method. A total of 90 yellow plaques were identified (b* =19.35+/-8.3, 3.05-45.35). Yellow plaques were significantly more prevalent in 14 (93%) of 15 culprit lesions of MI as compared with 8 (57%) of 14 of SA (p=0.03). In non-culprit segments, yellow plaques were similarly prevalent in 13 (87%) patients with MI and 11 (79%) with SA (p=0.65). Overall, multiple (> or =2) yellow plaques were prevalent in 13 (87%) patients with MI, similar to the 10 (71%) with SA (p=0.38). The number of yellow plaques was significantly higher in patients with MI (3.8+/-1.9) than in those with SA (2.4+/-1.6, p=0.03). The present study suggests that patients with MI tend to have diffuse atherosclerotic plaque in their coronary arteries.

Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries.

Science.gov (United States)

Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald S A

2008-08-01

The mechanisms of ectopic bone formation in arteries are poorly understood. Osteoblasts might originate either from stem cells that penetrate atherosclerotic plaques from the blood stream or from pluripotent mesenchymal cells that have remained in the arterial wall from embryonic stages of the development. We have examined the frequency of the expression and spatial distribution of osteoblast-specific factor-2/core binding factor-1 (Osf2/Cbfa1) in carotid and coronary arteries. Cbfa1-expressing cells were rarely observed but were found in all tissue specimens in the deep portions of atherosclerotic plaques under the necrotic cores. The deep portions of atherosclerotic plaques under the necrotic cores were characterized by the lack of capillaries of neovascularization. In contrast, plaque shoulders, which were enriched by plexuses of neovascularization, lacked Cbfa1-expressing cells. No bone formation was found in any of the 21 carotid plaques examined and ectopic bone was observed in only two of 12 coronary plaques. We speculate that the sparse invasion of sprouts of neovascularization into areas underlying the necrotic cores, where Cbfa1-expressing cells reside, might explain the rarity of events of ectopic bone formation in the arterial wall. This study has also revealed that Cbfa1-expressing cells contain alpha-smooth muscle actin and myofilaments, indicating their relationship with arterial smooth muscle cells.

Intravascular photoacoustic imaging: a new tool for vulnerable plaque identification.

Science.gov (United States)

Jansen, Krista; van Soest, Gijs; van der Steen, Antonius F W

2014-06-01

The vulnerable atherosclerotic plaque is believed to be at the root of the majority of acute coronary events. Even though the exact origins of plaque vulnerability remain elusive, the thin-cap fibroatheroma, characterized by a lipid-rich necrotic core covered by a thin fibrous cap, is considered to be the most prominent type of vulnerable plaque. No clinically available imaging technique can characterize atherosclerotic lesions to the extent needed to determine plaque vulnerability prognostically. Intravascular photoacoustic imaging (IVPA) has the potential to take a significant step in that direction by imaging both plaque structure and composition. IVPA is a natural extension of intravascular ultrasound that adds tissue type specificity to the images. IVPA utilizes the optical contrast provided by the differences in the absorption spectra of plaque components to image composition. Its capability to image lipids in human coronary atherosclerosis has been shown extensively ex vivo and has recently been translated to an in vivo animal model. Other disease markers that have been successfully targeted are calcium and inflammatory markers, such as macrophages and matrix metalloproteinase; the latter two through application of exogenous contrast agents. By simultaneously displaying plaque morphology and composition, IVPA can provide a powerful prognostic marker for disease progression, and as such has the potential to transform the current practice in percutaneous coronary intervention. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Differences in coronary plaque composition with aging measured by coronary computed tomography angiography.

Science.gov (United States)

Tota-Maharaj, Rajesh; Blaha, Michael J; Rivera, Juan J; Henry, Travis S; Choi, Eue-Keun; Chang, Sung-A; Yoon, Yeonyee E; Chun, Eun Ju; Choi, Sang-Il; Blumenthal, Roger S; Chang, Hyuk-Jae; Nasir, Khurram

2012-07-12

Little is known about the independent impact of aging on coronary plaque morphology and composition in the era of cardiac computed tomography angiography (CCTA). We studied 1015 consecutive asymptomatic South Korean subjects (49 ± 10 years, 64% men) who underwent 64-slice CCTA during routine health evaluation. Coronary plaque characteristics were analyzed on a per-segment basis according to the modified AHA classification. Plaques with >50% calcified tissue were classified as calcified (CAP), plaques with NCAP). Multiple regression analysis was employed to describe the cross-sectional association between age tertile and plaque type burden (≥ 2 affected segments) after adjustment for other cardiovascular risk factors. The prevalence of coronary plaque increased with age, (1st tertile: 7.5%, 3rd tertile: 38.5% [pNCAP to overall plaque burden decreased with age from nearly 50% in the first tertile to approximately 20% in the third, while there was a reciprocal increase in both MCAP and CAP subtypes. In multivariable analysis, patients in the oldest tertile had a 2.5-fold increase in burden of NCAP, yet a nearly 40-fold increase in MCAP and 16-fold increase in CAP compared to the youngest tertile. In conclusion, CCTA is an effective method for measuring age-related differences in the burden of individual coronary plaque subtypes. Future research is needed to determine whether the increase in mixed and calcified plaques seen with aging produce an independent contribution to the age-related increase in cardiovascular risk. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Rupture of the atherosclerotic plaque: does a good animal model exist?

NARCIS (Netherlands)

Cullen, Paul; Baetta, Roberta; Bellosta, Stefano; Bernini, Franco; Chinetti, Giulia; Cignarella, Andrea; von Eckardstein, Arnold; Exley, Andrew; Goddard, Martin; Hofker, Marten; Hurt-Camejo, Eva; Kanters, Edwin; Kovanen, Petri; Lorkowski, Stefan; McPheat, William; Pentikäinen, Markku; Rauterberg, Jürgen; Ritchie, Andrew; Staels, Bart; Weitkamp, Benedikt; de Winther, Menno

2003-01-01

By its very nature, rupture of the atherosclerotic plaque is difficult to study directly in humans. A good animal model would help us not only to understand how rupture occurs but also to design and test treatments to prevent it from happening. However, several difficulties surround existing models

DECT evaluation of noncalcified coronary artery plaque

Energy Technology Data Exchange (ETDEWEB)

Ravanfar Haghighi, Rezvan [Medical Imaging Research Center and Colorectal Research Center, Shiraz University of Medical Science, Shiraz 719 363 5899 (Iran, Islamic Republic of); Chatterjee, S. [BGVS Chemical Engineering Building (Old), Indian Institute of Science, Bangalore 560012 (India); Tabin, Milo; Singh, Rishi P.; Sharma, Munish; Krishna, Karthik [Department of Forensic Medicine, All India Institute of Medical Sciences, New Delhi 110029 (India); Sharma, Sanjiv; Jagia, Priya [Department of Cardiac-Radiology, All India Institute of Medical Sciences, New Delhi 110029 (India); Ray, Ruma; Arava, Sudhir [Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029 (India); Yadav, Rakesh [Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029 (India); Vani, V. C. [Department of Instrumentation and Applied Physics, Indian Institute of Science, Bangalore 560012 (India); Lakshmi, R.; Kumar, Pratik, E-mail: drpratikkumar@gmail.com [Department of Cardiac-Biochemistry, All India Institute of Medical Sciences, New Delhi 110029 (India); Mandal, Susama R. [Department of Medical Physics Unit IRCH, All India Institute of Medical Sciences, New Delhi 110029 (India)

2015-10-15

Purpose: Composition of the coronary artery plaque is known to have critical role in heart attack. While calcified plaque can easily be diagnosed by conventional CT, it fails to distinguish between fibrous and lipid rich plaques. In the present paper, the authors discuss the experimental techniques and obtain a numerical algorithm by which the electron density (ρ{sub e}) and the effective atomic number (Z{sub eff}) can be obtained from the dual energy computed tomography (DECT) data. The idea is to use this inversion method to characterize and distinguish between the lipid and fibrous coronary artery plaques. Methods: For the purpose of calibration of the CT machine, the authors prepare aqueous samples whose calculated values of (ρ{sub e}, Z{sub eff}) lie in the range of (2.65 × 10{sup 23} ≤ ρ{sub e} ≤ 3.64 × 10{sup 23}/cm{sup 3}) and (6.80 ≤ Z{sub eff} ≤ 8.90). The authors fill the phantom with these known samples and experimentally determine HU(V{sub 1}) and HU(V{sub 2}), with V{sub 1},V{sub 2} = 100 and 140 kVp, for the same pixels and thus determine the coefficients of inversion that allow us to determine (ρ{sub e}, Z{sub eff}) from the DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by filling the channel of the coronary artery with a viscous solution of methyl cellulose in water, containing 2% contrast. These (ρ{sub e}, Z{sub eff}) values of the coronary artery plaque are used for their characterization on the basis of theoretical models of atomic compositions of the plaque materials. These results are compared with histopathological report. Results: The authors find that the calibration gives ρ{sub e} with an accuracy of ±3.5% while Z{sub eff} is found within ±1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are found to be considerably different for the same plaque at the same position and there is a linear trend between these two HU values. It is noted that pure lipid type plaques

Atherosclerotic plaque destabilization in Mice: A comparative study

NARCIS (Netherlands)

H. Hartwig (Helene); C. Silvestre-Roig (Carlos); J. Hendrikse (Jeffrey); L. Beckers (Linda); N. Paulin (Nicole); K. van der Heiden (Kim); Q. Braster (Quinte); M. Drechsler (Maik); M.J. Daemen (Mat); E. Lutgens; O. Soehnlein (Oliver)

2015-01-01

textabstractAtherosclerosis-Associated diseases are the main cause ofmortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions thatmay become rupture-prone vulnerable plaques. Acute coronary syndromes are the

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

DEFF Research Database (Denmark)

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

2014-01-01

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

Atherosclerotic Plaque Destabilization in Mice: A Comparative Study

NARCIS (Netherlands)

Hartwig, Helene; Silvestre-Roig, Carlos; Hendrikse, Jeffrey; Beckers, Linda; Paulin, Nicole; van der Heiden, Kim; Braster, Quinte; Drechsler, Maik; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

2015-01-01

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

Coronary atherosclerosis in sudden cardiac death: An autopsy study

Directory of Open Access Journals (Sweden)

Sudha M

2009-10-01

Full Text Available Background: The incidence of ischemic heart disease (IHD has markedly increased in India over the past few years. Considering the variations in racial, dietary and lifestyle patterns in our population, it is essential to study the biology of coronary atherosclerosis in our patients. Vulnerable plaques have a large number of foam cells, extracellular lipid, thin fibrous caps and clusters of inflammatory cells and are more prone to rupture. These plaques are nourished by the microvessels arising from the vasa vasorum of the blood vessels and by lumen-derived microvessels through the fibrous cap. This autopsy study was designed to analyse the coronary arterial tree in cases of sudden cardiac death, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification and microvascular density. Materials and Methods: Seven cases of sudden cardiac death were included in the study. The hearts were perfusion-fixed and the coronary arteries along with their main branches were dissected and studied. The location of the plaques, type of plaques, presence of inflammation and calcification were assessed. The cap thickness and microvessel density per 1000um 2 were assessed. The statistical significance was estimated. Results and Conclusions: Extensive high-grade coronary atherosclerotic disease was seen in all sudden cardiac death cases. Majority of the plaques were vulnerable. High-grade inflammation was seen in most of the vulnerable and ruptured plaques. All the ruptured plaques were uncalcified indicating that calcification probably stabilizes the plaques and protects against rupture. Increased microvessel density was noted in ruptured plaques compared to vulnerable plaques. However, it was not statistically significant.

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

Science.gov (United States)

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

2014-06-01

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

Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging (the AQUAMARINE EPA/DHA study): study protocol for a randomized controlled trial.

Science.gov (United States)

Nakao, Kazuhiro; Noguchi, Teruo; Asaumi, Yasuhide; Morita, Yoshiaki; Kanaya, Tomoaki; Fujino, Masashi; Hosoda, Hayato; Yoneda, Shuichi; Kawakami, Shoji; Nagai, Toshiyuki; Nishihira, Kensaku; Nakashima, Takahiro; Kumasaka, Reon; Arakawa, Tetsuo; Otsuka, Fumiyuki; Nakanishi, Michio; Kataoka, Yu; Tahara, Yoshio; Goto, Yoichi; Yamamoto, Haruko; Hamasaki, Toshimitsu; Yasuda, Satoshi

2018-01-08

Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.

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

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Barros, Marcio Vinicius Lins; Siqueira, Bruna Pinto; Guimaraes, Carolina Camargos Braichi; Cruz, David Filipe Silva; Guimaraes, Leiziane Assuncao Alves; Lima, Maicom Marcio Perigolo, E-mail: marciovlbarros@gmail.com [Faculdade de Saude e Ecologia Humana, Vespasiano, MG (Brazil); Nunes, Maria do Carmo Pereira [Universidade de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Siqueira, Maria Helena Albernaz [Hospital Materdei, Belo Horizonte, MG (Brazil)

2015-07-15

Introduction: Although studies have shown high diagnostic accuracy of coronary tomography (CT) in detecting coronary artery disease (CAD), data on the prognostic value of this method in patients with no significant coronary obstruction are limited. Objective: To evaluate the value of CT in predicting adverse events in patients with suspected CAD and no significant coronary obstruction. Methods: We prospectively evaluated 440 patients between January 2008 and July 2013 by MDCT, diagnosed with no significant obstruction or no atherosclerotic coronary obstruction with an average follow-up of 33 months. The outcomes evaluated were: cardiac death, myocardial infarction, unstable angina associated with hospitalization or coronary artery bypass grafting. Results: Of the 440 patients studied, 295 (67%) were men with mean age 55.9 ± 12.0 years. Non-significant obstruction was found in 152 (35%) of the patients and there were 49 (11%) outcomes. In the multivariate analysis using the Cox regression model, the predictors of clinical outcomes were non-significant obstruction on CT (hazard ratio 3.51; 95% CI 1.73 - 7.8; p <0.01), age and hypertension. Non-significant obstruction on CT was associated with adverse clinical outcomes and survival analysis showed a significant difference (log-rank 24.6; p <0.01) in predicting these outcomes. Conclusion: The detection of non-significant atherosclerotic obstruction by CT was associated with the presence of adverse events in patients with suspected CAD, which may prove useful in the risk stratification of these patients. (author)

Comparative study of coronary plaque and stenosis: CT versus MR angiography

International Nuclear Information System (INIS)

Liu Xin; Zhao Xihai; Cheng Liuquan; Zhao Shaohong; Cai Zulong; Cai Youquan; Yang Li

2006-01-01

Objective: To investigate the effect of coronary plaque composition on the extent of stenosis and compare the accuracies of coronary CTA and MRA in detecting significant stenosis (≥50%) caused by different composition plaques. Methods: Thirty patients with coronary heart disease were examined with coronary CTA, MRA and conventional coronary, angiography (CAG) within two weeks. CTA and MRA were performed with a 16-slice CT scanner and hreathhold 3D FIESTA sequence respectively. The coronary plaques were grouped as non-calcified and calcified plaque on CTA images. The accuracies and agreement of CTA and MRA in detecting significant stenosis were evaluated by two experienced radiologists independently using CAG as reference. Results: Fifty-three plaques were detected on CTA. Twenty-eight were non-calcified and the other 25 were calcified. Twenty-one of 28 non-calcified plaques caused significant stenosis on CAG. The sensitivity and specificity of CTA and MRA in detecting significant stenosis were 85.7%, 85.7% and 47.6%, 71.4%, respectively, CTA showed good agreement with CAG (K=0.65). Six of 25 calcified plaques caused significant stenosis on CAG. The sensitivity and specificity of CTA and MRA in detecting significant stenosis were 83.3%, 31.6% and 83.3%, 73.7%, respectively, MRA showed moderate agreement with CAG (K=0.46). Conclusion: CTA was accurate for detecting non-calcified plaque and stenosis, while MRA had advantage to evaluate lumen with severe calcified plaque. (authors)

Calcified carotid atherosclerotic plaques on digital panoramic radiographs in patients with Type II diabetes mellitus: A case control study

Directory of Open Access Journals (Sweden)

Neha Khambete

2015-01-01

Full Text Available Aim: Diabetes mellitus is associated with accelerated carotid artery atherosclerosis and increased risk of stroke. This study was conducted with the objective of determining the prevalence of calcified atherosclerotic plaques on panoramic radiographs of patients with Type II diabetes mellitus. Materials and Methods: Panoramic radiographs of 100 patients (age range 50-84 years with known history of type II diabetes mellitus, visiting the outpatient department were evaluated for the presence of calcified atherosclerotic plaques. Age- and sex-matched controls were evaluated in the same manner. Statistical comparison of prevalence rates was done. Results: The radiographs of diabetics (mean age: 64.45 years revealed that 26% had atheromatous plaques, whereas those of controls (mean age: 65.36 years revealed that 6% had atheromatous plaques. A statistically significant difference (P = 0.01410 was obtained using Yates′ Chi-square test. Conclusion: People with diabetes mellitus had a greater prevalence of calcified atherosclerotic plaques on panoramic radiographs than non-diabetics. Panoramic radiographs of diabetic patients should be screened for the presence of carotid artery atheromatous plaques for timely medical referral of asymptomatic patients and avoiding any further serious consequences like cerebrovascular accidents.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

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

Science.gov (United States)

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

2017-10-05

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

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

International Nuclear Information System (INIS)

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

2016-01-01

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

Progress in genetics of coronary artery disease

African Journals Online (AJOL)

Radwa Gamal

To the Editor. Coronary Heart Disease (CHD) is the leading cause of mortality and morbidity worldwide [1] and it is a result of coronary artery disease (CAD). Coronary artery disease refers to the build-up of atherosclerotic plaque in the blood vessels that supply oxygen and nutrients to the heart. Progressive infiltration of the ...

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Viral Heart Disease and Acute Coronary Syndromes - Often or Rare Coexistence?

Science.gov (United States)

Pawlak, Agnieszka; Wiligorska, Natalia; Wiligorska, Diana; Frontczak-Baniewicz, Malgorzata; Przybylski, Maciej; Krzyzewski, Rafal; Ziemba, Andrzej; Gil, Robert J

2018-01-01

Clinical presentation of viral myocarditis can mimic acute coronary syndrome and making diagnosis of viral heart disease (VHD) may be challenging. The presence of coronary artery disease (CAD) does not always exclude VHD and these entities can coexist. However, the incidence of co-occurrence of CAD and VHD is not precisely known. Moreover, inflammatory process caused by viruses may result in atherosclerotic plaque destabilization. The goal of this work is to summarize the current knowledge about co-occurrence of VHD and CAD. This article presents the importance of inflammatory process in both diseases and helps to understand pathophysiological mechanisms underlying their coexistence. It provides information about making differential diagnosis between these entities, including clinical presentation, noninvasive imaging features and findings in endomyocardial biopsy. Although currently there are no standard therapy strategies in coexistence of VHD and CAD, we present some remarkable aspects of treatment of patients, in whom VHD co-occurs with CAD. Viral heart disease may occur both in patients without and with atherosclerotic plaques in coronary arteries. Destabilization of atherosclerotic plaques in coronary arteries can be facilitated by inflammatory process. Increased inflammatory infiltrates in the coronary lesions of patients with VHD can lead to plaques' instability and consequently trigger acute coronary syndrome. In this article we attempted to present that co-occurrence of VHD and CAD may have therapeutic implications and as specific antiviral treatment is currently available, proper diagnosis and treatment can improve patient's condition and prognosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Invasive or non-invasive imaging for detecting high-risk coronary lesions?

NARCIS (Netherlands)

K. Patel (Kush); J. Tarkin (Jason); P.W.J.C. Serruys (Patrick); E. Tenekecioglu (Erhan); N. Foin (Nicolas); Y. Zhang (Yaojun); T. Crake (Tom); J. Moon (James); A. Mathur (Anthony); C.V. Bourantas (Christos)

2017-01-01

markdownabstract_Introduction:_ Advances in our understanding about atherosclerotic evolution have enabled us to identify specific plaque characteristics that are associated with coronary plaque vulnerability and cardiovascular events. With constant improvements in signal and image processing an

Impact of Pre-Diabetes on Coronary Plaque Composition and Clinical Outcome in Patients With Acute Coronary Syndromes: An Analysis From the PROSPECT Study.

Science.gov (United States)

Farhan, Serdar; Redfors, Björn; Maehara, Akiko; McAndrew, Thomas; Ben-Yehuda, Ori; De Bruyne, Bernard; Mehran, Roxana; Giustino, Gennaro; Kirtane, Ajay J; Serruys, Patrick W; Mintz, Gary S; Stone, Gregg W

2017-10-14

The aim of this study was to investigate the impact of pre-diabetes (pre-DM) on coronary plaque characteristics and ischemic outcomes in patients with acute coronary syndromes (ACS). Pre-DM (i.e., the early stages of glucometabolic disturbance) is common among patients with ACS, but the extent to which pre-DM influences coronary plaque characteristics and the risk for adverse ischemic events is unclear. In the PROSPECT (Providing Regional Observations to Study Predictors of Events in Coronary Tree) study, patients with ACS underwent quantitative coronary angiography, grayscale intravascular ultrasound, and radiofrequency intravascular ultrasound after successful percutaneous coronary intervention. Patients were divided into 3 groups according to their glucometabolic status, as defined by the American Diabetes Association: normal glucose metabolism (NGM), pre-DM, and diabetes mellitus (DM). These groups were compared with regard to coronary plaque characteristics and the risk for major adverse cardiac events (MACEs) (defined as cardiac death or arrest, myocardial infarction, or rehospitalization for unstable or progressive angina). Among 547 patients, 162 (29.6%) had NGM, 202 (36.9%) had pre-DM, and 183 (33.4%) had DM. There were no significant differences between the groups with regard to intravascular ultrasound findings indicative of vulnerable plaques. Patients with DM had a higher crude rate of MACEs than those with pre-DM or NGM (25.9% vs. 16.3% and 16.1%; p = 0.03 and p = 0.02, respectively). In an adjusted Cox regression model using NGM as the reference group, DM (hazard ratio: 2.20; 95% confidence interval: 1.25 to 3.86; p = 0.006) but not pre-DM (hazard ratio: 1.29; 95% confidence interval: 0.71 to 2.33; p = 0.41) was associated with increased risk for MACEs. Impaired glucose metabolism is common among patients presenting with ACS. DM but not pre-DM is associated with an increased risk for MACEs. Thus, preventing patients from progressing from pre

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.

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.)

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

International Nuclear Information System (INIS)

Noerenberg, Dominik; Ebersberger, Hans U.; Diederichs, Gerd; Hamm, Bernd; Botnar, Rene M.; Makowski, Marcus R.

2016-01-01

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.)

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.

Coronary plaque property evaluation by coronary CTA and its correlation with inflammatory molecules and MMPs/TIMPs

Directory of Open Access Journals (Sweden)

Wen-Bing Yang

2017-11-01

Full Text Available Objective: To study the evaluation value of coronary CTA for coronary plaque properties and its correlation with inflammatory molecules and MMPs/TIMPs. Methods: Patients who were diagnosed with acute coronary syndrome in Renmin Hospital of Wuhan University between August 2014 and December 2016 were selected as the ACS group of the research, patients who were diagnosed with stable angina pectoris were selected as the SAP group of the research, and healthy subjects who received physical examination during the same period were selected as the control group of the research. Coronary CTA was done to determine the coronary plaque properties of ACS group, and serum was collected from the three groups of subjects to determine the contents of inflammatory molecules and MMPs/TIMPs collagen metabolites. Results: Serum MIP-1α, MCP-1, sFGL-2, sCD14, CXCL5, I-CTP, III-CTP and EMMPRIN contents of ACS group and SAP group were higher than those of control group while TIMP1, TIMP2 contents were lower than those of control group; serum MIP-1α, MCP-1, sFGL-2, sCD14, CXCL5, I-CTP, III-CTP and EMMPRIN contents of ACS group were higher than those of SAP group while TIMP1 and TIMP2 contents were lower than those of SAP group. Serum MIP-1α, MCP-1, sFGL-2, sCD14, CXCL5, I-CTP, III-CTP and EMMPRIN contents of ACS patients with soft plaque and fibrous plaque were higher than those of ACS patients with calcified plaque while TIMP1 and TIMP2 contents were lower than those of ACS patients with calcified plaque; serum MIP-1α, MCP-1, sFGL-2, sCD14, CXCL5, I-CTP, III-CTP and EMMPRIN contents of ACS patients with soft plaque were higher than those of ACS patients with fibrous plaque while TIMP1, TIMP2 contents were lower than those of ACS patients with fibrous plaque. Conclusion: The coronary plaque property evaluation by coronary CTA is closely related to the changes of inflammatory response and MMPs/TIMPs collagen metabolism.

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

DEFF Research Database (Denmark)

Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

2013-01-01

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

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

NARCIS (Netherlands)

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

2011-01-01

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

Gene expression and 18FDG uptake in atherosclerotic carotid plaques

DEFF Research Database (Denmark)

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

2010-01-01

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

An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

Science.gov (United States)

Maggi, Paolo; Perilli, Francesco; Lillo, Antonio; Carito, Valentina; Epifani, Giuseppe; Bellacosa, Chiara; Pastore, Giuseppe; Regina, Guido

2007-02-01

We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.

Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery

NARCIS (Netherlands)

Pasterkamp, G.; Schoneveld, A. H.; Hijnen, D. J.; de Kleijn, D. P.; Teepen, H.; van der Wal, A. C.; Borst, C.

2000-01-01

Atherosclerotic luminal narrowing is determined by plaque mass and the mode of geometrical remodeling. Recently, we reported that the type of atherosclerotic remodeling is associated with the presence of histological markers for plaque vulnerability. Inflammation and matrix degrading proteases

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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.)

Mechanisms of erosion of atherosclerotic plaques.

Science.gov (United States)

Quillard, Thibaut; Franck, Grégory; Mawson, Thomas; Folco, Eduardo; Libby, Peter

2017-10-01

The present review explores the mechanisms of superficial intimal erosion, a common cause of thrombotic complications of atherosclerosis. Human coronary artery atheroma that give rise to thrombosis because of erosion differ diametrically from those associated with fibrous cap rupture. Eroded lesions characteristically contain few inflammatory cells, abundant extracellular matrix, and neutrophil extracellular traps (NETs). Innate immune mechanisms such as engagement of Toll-like receptor 2 (TLR2) on cultured endothelial cells can impair their viability, attachment, and ability to recover a wound. Hyaluronan fragments may serve as endogenous TLR2 ligands. Mouse experiments demonstrate that flow disturbance in arteries with neointimas tailored to resemble features of human eroded plaques disturbs endothelial cell barrier function, impairs endothelial cell viability, recruits neutrophils, and provokes endothelial cells desquamation, NET formation, and thrombosis in a TLR2-dependent manner. Mechanisms of erosion have received much less attention than those that provoke plaque rupture. Intensive statin treatment changes the characteristic of plaques that render them less susceptible to rupture. Thus, erosion may contribute importantly to the current residual burden of risk. Understanding the mechanisms of erosion may inform the development and deployment of novel therapies to combat the remaining atherothrombotic risk in the statin era.

Italian Chapter of the International Society of Cardiovascular Ultrasound expert consensus document on coronary computed tomography angiography: overview and new insights.

Science.gov (United States)

Sozzi, Fabiola B; Maiello, Maria; Pelliccia, Francesco; Parato, Vito Maurizio; Canetta, Ciro; Savino, Ketty; Lombardi, Federico; Palmiero, Pasquale

2016-09-01

Coronary computed tomography angiography is a noninvasive heart imaging test currently undergoing rapid development and advancement. The high resolution of the three-dimensional pictures of the moving heart and great vessels is performed during a coronary computed tomography to identify coronary artery disease and classify patient risk for atherosclerotic cardiovascular disease. The technique provides useful information about the coronary tree and atherosclerotic plaques beyond simple luminal narrowing and plaque type defined by calcium content. This application will improve image-guided prevention, medical therapy, and coronary interventions. The ability to interpret coronary computed tomography images is of utmost importance as we develop personalized medical care to enable therapeutic interventions stratified on the bases of plaque characteristics. This overview provides available data and expert's recommendations in the utilization of coronary computed tomography findings. We focus on the use of coronary computed tomography to detect coronary artery disease and stratify patients at risk, illustrating the implications of this test on patient management. We describe its diagnostic power in identifying patients at higher risk to develop acute coronary syndrome and its prognostic significance. Finally, we highlight the features of the vulnerable plaques imaged by coronary computed tomography angiography. © 2016, Wiley Periodicals, Inc.

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

Influence of Adaptive Statistical Iterative Reconstruction on coronary plaque analysis in coronary computed tomography angiography.

Science.gov (United States)

Precht, Helle; Kitslaar, Pieter H; Broersen, Alexander; Dijkstra, Jouke; Gerke, Oke; Thygesen, Jesper; Egstrup, Kenneth; Lambrechtsen, Jess

The purpose of this study was to study the effect of iterative reconstruction (IR) software on quantitative plaque measurements in coronary computed tomography angiography (CCTA). Thirty patients with a three clinical risk factors for coronary artery disease (CAD) had one CCTA performed. Images were reconstructed using FBP, 30% and 60% adaptive statistical IR (ASIR). Coronary plaque analysis was performed as per patient and per vessel (LM, LAD, CX and RCA) measurements. Lumen and vessel volumes and plaque burden measurements were based on automatic detected contours in each reconstruction. Lumen and plaque intensity measurements and HU based plaque characterization were based on corrected contours copied to each reconstruction. No significant changes between FBP and 30% ASIR were found except for lumen- (-2.53 HU) and plaque intensities (-1.28 HU). Between FBP and 60% ASIR the change in total volume showed an increase of 0.94%, 4.36% and 2.01% for lumen, plaque and vessel, respectively. The change in total plaque burden between FBP and 60% ASIR was 0.76%. Lumen and plaque intensities decreased between FBP and 60% ASIR with -9.90 HU and -1.97 HU, respectively. The total plaque component volume changes were all small with a maximum change of -1.13% of necrotic core between FBP and 60% ASIR. Quantitative plaque measurements only showed modest differences between FBP and the 60% ASIR level. Differences were increased lumen-, vessel- and plaque volumes, decreased lumen- and plaque intensities and a small percentage change in the individual plaque component volumes. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

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.

Evaluation value of coronary CTA for coronary plaque features and its correlation with platelet function and serum biochemical indexes

Directory of Open Access Journals (Sweden)

Jin-Xia Yang

2017-01-01

Full Text Available Objective: To analyze the evaluation value of coronary CT angiography for coronary plaque features and its correlation with platelet function and serum biochemical indexes. Methods: A total of 450 patients with coronary heart disease were divided into calcified plaque group (CT value≥130HU (n=117, soft plaque group (CT value≤60HU (n=150 and mixed plaque group (CT value 60-130HU (n=183 by coronary CT angiography (CTA, and 100 healthy subjects who received physical examination in our hospital during the same period were selected as control group. Differences in platelet function and serum biochemical indexes were compared among four groups of patients, and the judgment value of atheromatous plaque CT value from CTA for the severity of coronary heart disease was analyzed. Results: Platelet function parameters MPV, TEG-MA, P-selectin, PDGF-BB and vWF levels in peripheral blood of soft plaque group were higher than those of the other three groups; inflammatory factors CRP, IL-6, IL-12, IL-18 and IL-23 content in serum were higher than those of the other three groups; chemokines MCP-1, CXCL16, Fractalkine and RANTES content in serum were higher than those of the other three groups; adipocytokines Leptin and RBP4 content in serum were higher than those of the other three groups while SFRP5 content was lower than those of the other three groups. Atheromatous plaque CT value in patients with coronary heart disease was directly correlated with platelet function and the content of serum biochemical indexes. Conclusions: Coronary CTA can accurately assess coronary atheromatous plaque features, and can also be a reliable noninvasive method to judge coronary heart disease severity, treatment prognosis and so on.

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...... deviation and autocorrelation) provide good correlation within the training set (p = 0.04); However, the correlation found so far is not so high, that the method can be used in clinical prediction of plaque constituents....

Radioiodinate labeling of atherosclerotic plaque imaging agent SP-4 and preliminary experiments

International Nuclear Information System (INIS)

Zhang, Y.; Wu, Z.

2000-01-01

SP-4 was oligopeptide contained 18 amino-acid. It was a part of apolipoprotein B. To study labeling SP-4 with 131 I and its clinical prospect as an atherosclerotic plaque imaging agent. SP-4 was synthesized by solid phase method and identified by amino acid analysis after purification with preparation-model HPLC. SP-4 was labeled with 131 I by the Chloramine-T method and purified through Sephadex G-25, then the radiochemical purity of 131 SP-4 and its stability in vitro were analyzed. 12 New Zealand rabbits were divided into atherosclerosis group (n=7, group A) and control group (n=5, group B). All of them were administrated with bovine serum albumen through i.v., then the rabbits of group A were fed on high cholesterol and high fat diet and group B, on normal diet. Purified 131 I-SP-4 was injected intravenously. %ID/g in blood and thoracic aorta and abdominal aorta at 4 hrs after injection and biodistribution of 131 I-SP-4 was investigated. The amino acid formation of the pure product was identified to be correct through amino-acid analysis. The radiochemical purity of 131 I-SP-4 was 96.2% after being purified, but less than 90% after being stored for 20 hrs. One of 7 rabbits in group A died after being fed for three weeks, the others were alive and atherosclerotic lesions were found after being fed for two mon. On the contrary, 5 rabbits in group B were visualized not to have atherosclerotic lesions. The uptakes of group A and group B at 4 hr after injection were 0.0378±0.0028 and 0.0371±0.038 in blood (p>0.05), 0.0882 ±0.0101 and 0.0276 ±0.0044 in abdominal aorta (p 131 I-SP-4 was mainly excreted through kidneys. SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions. It was potentially useful as an atherosclerotic plaque imaging agent

High-risk carotid plaques identified by CT-angiogram can predict acute myocardial infarction.

Science.gov (United States)

Mosleh, Wassim; Adib, Keenan; Natdanai, Punnanithinont; Carmona-Rubio, Andres; Karki, Roshan; Paily, Jacienta; Ahmed, Mohamed Abdel-Aal; Vakkalanka, Sujit; Madam, Narasa; Gudleski, Gregory D; Chung, Charles; Sharma, Umesh C

2017-04-01

Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3 mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.

TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE−/− mice

Science.gov (United States)

Prasad, Sakamuri Siva Sankara Vara; Higashi, Yusuke; Sukhanov, Sergiy; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Chandrasekar, Bysani

2016-01-01

Background and aims Atherosclerosis is a major cause of heart attack and stroke. Inflammation plays a critical role in the development of atherosclerosis. Since the cytoplasmic adaptor molecule TRAF3IP2 (TRAF3-Interacting Protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that TRAF3IP2 mediates atherosclerotic plaque development. Methods TRAF3IP2/ApoE double knockout (DKO) mice were generated by crossing TRAF3IP2−/− and ApoE−/− mice. ApoE−/− mice served as controls. Both DKO and control mice were fed a high-fat diet for 12 weeks. Plasma lipids were measured by ELISA, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell content by histomorphometry, and aortic gene expression by RT-qPCR. Results The plasma lipoprotein profile was not altered by TRAF3IP2 gene deletion in ApoE−/− mice. While total aortic plaque area was decreased in DKO female, but not male mice, the plaque necrotic area was significantly decreased in DKO mice of both genders. Plaque collagen and smooth muscle cell contents were increased significantly in both female and male DKO mice compared to respective controls. Aortic expression of proinflammatory cytokine (Tumor necrosis factor α, TNFα), chemokine (Chemokine (C-X-C motif) Ligand 1, CXCL1) and adhesion molecule (Vascular cell adhesion molecule 1, VCAM1; and Intercellular adhesion molecule 1, ICAM1) gene expression were decreased in both male and female DKO mice. In addition, the male DKO mice showed a markedly reduced expression of extracellular matrix (ECM)-related genes, including TIMP1 (Tissue inhibitor of metalloproteinase 1), RECK (Reversion-Inducing- Cysteine-Rich Protein with Kazal Motifs) and ADAM17 (A Disintegrin And Metalloproteinase 17). Conclusions TRAF3IP2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the

Tyrosine phosphorylation of platelet derived growth factor β receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris

Science.gov (United States)

Abe, J; Deguchi, J; Takuwa, Y; Hara, K; Ikari, Y; Tamura, T; Ohno, M; Kurokawa, K

1998-01-01

Background—Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.
Aims—To investigate whether the concentration of PDGF β receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.
Methods—DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.
Results—PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p atherectomy;  restenosis PMID:9616351

Association between increased epicardial adipose tissue volume and coronary plaque composition.

Science.gov (United States)

Yamashita, Kennosuke; Yamamoto, Myong Hwa; Ebara, Seitarou; Okabe, Toshitaka; Saito, Shigeo; Hoshimoto, Koichi; Yakushiji, Tadayuki; Isomura, Naoei; Araki, Hiroshi; Obara, Chiaki; Ochiai, Masahiko

2014-09-01

To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or calcified tissue, based on the radiofrequency spectrum. Epicardial adipose tissue was measured as the tissue ranging from -190 to -30 Hounsfield units. EATV, calculated as the sum of the fat areas on short-axis images, was 85.0 ± 34.0 cm(3). There was a positive correlation between EATV and the percentage of necrotic plaque tissue (R (2) = 0.34, P EATV and the percentage of fibrous tissue (R (2) = 0.24, P EATV (β = 0.14, P = 0.02) were independently associated with the percentage of necrotic plaque tissue. An increase in EATV was associated with the development of coronary atherosclerosis and, potentially, with the most dangerous type of plaque.

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

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

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

International Nuclear Information System (INIS)

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

2003-01-01

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

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

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......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...

Plaque disruption by coronary computed tomographic angiography in stable patients vs. acute coronary syndrome: a feasibility study.

Science.gov (United States)

Bilolikar, Abhay N; Goldstein, James A; Madder, Ryan D; Chinnaiyan, Kavitha M

2016-03-01

This study was designed to determine whether coronary CT angiography (CTA) can detect features of plaque disruption in clinically stable patients and to compare lesion prevalence and features between stable patients and those with acute coronary syndrome (ACS). We retrospectively identified patients undergoing CTA, followed by invasive coronary angiography (ICA) within 60 days. Quantitative 3-vessel CTA lesion analysis was performed on all plaques ≥25% stenosis to assess total plaque volume, low attenuation plaque (LAP, disruption, including ulceration and intra-plaque dye penetration (IDP). ICA was employed as a reference standard for disruption. A total of 145 (94 ACS and 51 stable) patients were identified. By CTA, plaque disruption was evident in 77.7% of ACS cases. Although more common among those with ACS, CTA also detected plaque disruption in 37.3% of clinically stable patients (P disruption as determined by CTA. Though the prevalence of plaque disruption is less than patients with ACS, these findings support the concept that some clinically stable patients may harbour 'silent' disrupted plaques. These findings may have implications for detection of 'at risk' plaques and patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Comparison of coronary arterial lumen dimensions on angiography and plaque characteristics on optical coherence tomography images and their changes induced by statin

International Nuclear Information System (INIS)

Dong, Nana; Xie, Zulong; Wang, Wei; Dai, Jiannan; Sun, Meng; Pu, Zhongyue; Tian, Jinwei; Yu, Bo

2016-01-01

Coronary angiography (CAG) is widely used to assess lumen dimensions, and optical coherence tomography (OCT) is used to evaluate the characteristics of atherosclerotic plaque. This study was aimed to compare coronary lumen dimensions using CAG and plaque characteristics using OCT and their changes during statin therapy. We identified 97 lipid-rich plaques from 69 statin-naïve patients, who received statin therapy in the following 12 months. CAG and OCT examinations were conducted at baseline and 12-month follow-up period. Lesion length, as measured by CAG, was closely correlated with lipid length by OCT (baseline: r = 0.754, p < 0.001; follow-up: r = 0.639, p < 0.001). However, no significant correlations were found between the other findings on OCT and data on CAG. With 12-month statin therapy, microstructures of lipid-rich plaques were significantly improved, but CAG-derived lumen dimensions were not improved. Moreover, we found no significant relationship between changes in OCT measurements and changes in CAG data over time. Lipid length on OCT and lesion length on CAG were closely correlated. However, plaque microstructural characteristics on OCT showed no significantly statistically correlations with lumen dimensions on CAG, neither did their evolutionary changes induced by statin over time. Clinical trial registry: ClinicalTrial.gov. Registered number: NCT01023607. Registered 1 December 2009

RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.

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Christian Herder

Full Text Available The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events.We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years. Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]. None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls, none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years.High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i RANTES serum levels, (ii CCL5 genotypes and (iii RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a

Association between increased epicardial adipose tissue volume and coronary plaque composition

OpenAIRE

Yamashita, Kennosuke; Yamamoto, Myong Hwa; Ebara, Seitarou; Okabe, Toshitaka; Saito, Shigeo; Hoshimoto, Koichi; Yakushiji, Tadayuki; Isomura, Naoei; Araki, Hiroshi; Obara, Chiaki; Ochiai, Masahiko

2013-01-01

To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or ...

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

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......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...

Analysis of Complex Coronary Plaque in Multidetector Computed Tomography: Comparison with Conventional Coronary Angiography

International Nuclear Information System (INIS)

Kim, Dong Hyun; Bang, Duck Won; Cho, Yoon Haeng; Suk, Eun Ha

2011-01-01

To delineate complex plaque morphology in patients with stable angina using coronary computed tomographic angiography (CTA). 36 patients with complex plaques proven by conventional coronary angiography (CAG), who had taken CTA for evaluation of typical angina, were enrolled in this study. Intravascular ultrasonography (IVUS) was performed in 14 patients (16 lesions). We compared CTA with CAG for plaque features and analyzed vascular cutoff, intraluminal filling defect in a patent vessel, irregularity of plaque, and ulceration. Also, the density of plaque was evaluated on CTA. CAG and CTA showed complex morphology in 44 cases (100%) and 34 cases, (77%), respectively, with features including abrupt vessel cutoff (27 vs. 16%, κ=0.57), intraluminal filling defect (32 vs. 30%, κ=0.77), irregularity (75 vs. 52%, κ=0.52), and ulceration (16 vs. 11%, κ=0.60). CTA indicated that the complex lesions were hypodense (mean 66 ± 21 Houndsfield Units). CTA is a very accurate and useful non-invasive imaging modality for evaluating complex plaque in patients with typical angina.

Analysis of Complex Coronary Plaque in Multidetector Computed Tomography: Comparison with Conventional Coronary Angiography

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Kim, Dong Hyun [Dept. of Radiology, Soonchunhyang University Hospital, Bucheon (Korea, Republic of); Bang, Duck Won; Cho, Yoon Haeng [Dept. of Internal Medicine, Soonchunhyang University Hospital, Bucheon (Korea, Republic of); Suk, Eun Ha [Dept. of Anesthyesiology and Pain Medicine, Asan Medical Center, Seoul (Korea, Republic of)

2011-04-15

To delineate complex plaque morphology in patients with stable angina using coronary computed tomographic angiography (CTA). 36 patients with complex plaques proven by conventional coronary angiography (CAG), who had taken CTA for evaluation of typical angina, were enrolled in this study. Intravascular ultrasonography (IVUS) was performed in 14 patients (16 lesions). We compared CTA with CAG for plaque features and analyzed vascular cutoff, intraluminal filling defect in a patent vessel, irregularity of plaque, and ulceration. Also, the density of plaque was evaluated on CTA. CAG and CTA showed complex morphology in 44 cases (100%) and 34 cases, (77%), respectively, with features including abrupt vessel cutoff (27 vs. 16%, {kappa}=0.57), intraluminal filling defect (32 vs. 30%, {kappa}=0.77), irregularity (75 vs. 52%, {kappa}=0.52), and ulceration (16 vs. 11%, {kappa}=0.60). CTA indicated that the complex lesions were hypodense (mean 66 {+-} 21 Houndsfield Units). CTA is a very accurate and useful non-invasive imaging modality for evaluating complex plaque in patients with typical angina.

Coronary CT: clinical indications and future directions

International Nuclear Information System (INIS)

Nomura, Cesar H.; Serpa, Bruna S.; Kay, Fernando U.; Szarf, Gilberto; Passos, Rodrigo B.; Neto, Roberto S.; Chate, Rodigo C.; Funar, Marcelo B.; Cury, Roberto C.

2011-01-01

Multidetector computed tomography (MDCT) has started its implementation in cardiology with calcium quantification of coronary plaques in the study without contrast, using the calcium score, demonstrating an important independent predictor of future cardiac events. The examination with intravenous contrast, coronary angiography, appeared later as a noninvasive method for evaluation of anatomy and obstructive coronary disease, characterizing the degree of stenosis and the presence of non calcified atherosclerotic plaques, assessing not only the lumen, but also the vessel wall. With the advent of new machines with more detectors and higher temporal resolution has been a reduction in radiation dose and the possibility of new applications. (author)

64Cu-Labeled LyP-1-Dendrimer for PET-CT Imaging of Atherosclerotic Plaque

Science.gov (United States)

2015-01-01

The ability to detect and quantify macrophage accumulation can provide important diagnostic and prognostic information for atherosclerotic plaque. We have previously shown that LyP-1, a cyclic 9-amino acid peptide, binds to p32 proteins on activated macrophages, facilitating the visualization of atherosclerotic plaque with PET. Yet, the in vivo plaque accumulation of monomeric [18F]FBA-LyP-1 was low (0.31 ± 0.05%ID/g). To increase the avidity of LyP-1 constructs to p32, we synthesized a dendritic form of LyP-1 on solid phase using lysine as the core structural element. Imaging probes (FAM or 6-BAT) were conjugated to a lysine or cysteine on the dendrimer for optical and PET studies. The N-terminus of the dendrimer was further modified with an aminooxy group in order to conjugate LyP-1 and ARAL peptides bearing a ketone. Oxime ligation of peptides to both dendrimers resulted in (LyP-1)4- and (ARAL)4-dendrimers with optical (FAM) and PET probes (6-BAT). For PET-CT studies, (LyP-1)4- and (ARAL)4-dendrimer-6-BAT were labeled with 64Cu (t1/2 = 12.7 h) and intravenously injected into the atherosclerotic (ApoE–/–) mice. After two hours of circulation, PET-CT coregistered images demonstrated greater uptake of the (LyP-1)4-dendrimer-64Cu than the (ARAL)4-dendrimer-64Cu in the aortic root and descending aorta. Ex vivo images and the biodistribution acquired at three hours after injection also demonstrated a significantly higher uptake of the (LyP-1)4-dendrimer-64Cu (1.1 ± 0.26%ID/g) than the (ARAL)4-dendrimer-64Cu (0.22 ± 0.05%ID/g) in the aorta. Similarly, subcutaneous injection of the LyP-1-dendrimeric carriers resulted in preferential accumulation in plaque-containing regions over 24 h. In the same model system, ex vivo fluorescence images within aortic plaque depict an increased accumulation and penetration of the (LyP-1)4-dendrimer-FAM as compared to the (ARAL)4-dendrimer-FAM. Taken together, the results suggest that the (LyP-1)4-dendrimer can be applied for in

[Plaque segmentation of intracoronary optical coherence tomography images based on K-means and improved random walk algorithm].

Science.gov (United States)

Wang, Guanglei; Wang, Pengyu; Han, Yechen; Liu, Xiuling; Li, Yan; Lu, Qian

2017-06-01

In recent years, optical coherence tomography (OCT) has developed into a popular coronary imaging technology at home and abroad. The segmentation of plaque regions in coronary OCT images has great significance for vulnerable plaque recognition and research. In this paper, a new algorithm based on K -means clustering and improved random walk is proposed and Semi-automated segmentation of calcified plaque, fibrotic plaque and lipid pool was achieved. And the weight function of random walk is improved. The distance between the edges of pixels in the image and the seed points is added to the definition of the weight function. It increases the weak edge weights and prevent over-segmentation. Based on the above methods, the OCT images of 9 coronary atherosclerotic patients were selected for plaque segmentation. By contrasting the doctor's manual segmentation results with this method, it was proved that this method had good robustness and accuracy. It is hoped that this method can be helpful for the clinical diagnosis of coronary heart disease.

Progranulin expression in advanced human atherosclerotic plaque.

Science.gov (United States)

Kojima, Yoji; Ono, Koh; Inoue, Katsumi; Takagi, Yasushi; Kikuta, Ken-ichiro; Nishimura, Masaki; Yoshida, Yoshinori; Nakashima, Yasuhiro; Matsumae, Hironobu; Furukawa, Yutaka; Mikuni, Nobuhiro; Nobuyoshi, Masakiyo; Kimura, Takeshi; Kita, Toru; Tanaka, Makoto

2009-09-01

Progranulin (PGRN) is a unique growth factor that plays an important role in cutaneous wound healing. It has an anti-inflammatory effect and promotes cell proliferation. However, when it is degraded to granulin peptides (GRNs) by neutrophil proteases, a pro-inflammatory reaction occurs. Since injury, inflammation and repair are common features in the progression of atherosclerosis, it is conceivable that PGRN plays a role in atherogenesis. Immunohistochemical analysis of human carotid endoatherectomy specimens indicated that vascular smooth muscle cells (vSMCs) in the intima expressed PGRN. Some macrophages in the plaque also expressed PGRN. We assessed the effect of PGRN on a human monocytic leukemia cell line (THP-1) and human aortic smooth muscle cells (HASMCs). PGRN alone had no effect on HASMC or THP-1 proliferation or migration. However, when THP-1 cells were stimulated with MCP-1, the number of migrated cells decreased in a PGRN-dose-dependent manner. TNF-alpha-induced HASMC migration was enhanced only at 10nM of PGRN. Interleukin-8 (IL-8) secretion from HASMCs was reduced by forced expression of PGRN and increased by RNAi-mediated knockdown of PGRN. While exogenous treatment with recombinant PGRN decreased IL-8 secretion, degraded recombinant GRNs increased IL-8 secretion from HASMCs. The expression of PGRN mainly reduces inflammation and its degradation into GRNs enhances inflammation in atherosclerotic plaque and may contribute to the progression of atherosclerosis.

Recent activation of the plaque immune response in coronary lesions underlying acute coronary syndromes

NARCIS (Netherlands)

van der Wal, A. C.; Piek, J. J.; de Boer, O. J.; Koch, K. T.; Teeling, P.; van der Loos, C. M.; Becker, A. E.

1998-01-01

OBJECTIVE: To discriminate between chronic inflammation and acute activation of the plaque immune response in culprit lesions of patients with acute coronary syndromes. DESIGN: Retrospective study. SETTING: Tertiary referral centre. SUBJECTS: 71 patients having coronary atherectomy were classified

CT coronary angiography: impact of adapted statistical iterative reconstruction (ASIR) on coronary stenosis and plaque composition analysis.

Science.gov (United States)

Fuchs, Tobias A; Fiechter, Michael; Gebhard, Cathérine; Stehli, Julia; Ghadri, Jelena R; Kazakauskaite, Egle; Herzog, Bernhard A; Husmann, Lars; Gaemperli, Oliver; Kaufmann, Philipp A

2013-03-01

To assess the impact of adaptive statistical iterative reconstruction (ASIR) on coronary plaque volume and composition analysis as well as on stenosis quantification in high definition coronary computed tomography angiography (CCTA). We included 50 plaques in 29 consecutive patients who were referred for the assessment of known or suspected coronary artery disease (CAD) with contrast-enhanced CCTA on a 64-slice high definition CT scanner (Discovery HD 750, GE Healthcare). CCTA scans were reconstructed with standard filtered back projection (FBP) with no ASIR (0 %) or with increasing contributions of ASIR, i.e. 20, 40, 60, 80 and 100 % (no FBP). Plaque analysis (volume, components and stenosis degree) was performed using a previously validated automated software. Mean values for minimal diameter and minimal area as well as degree of stenosis did not change significantly using different ASIR reconstructions. There was virtually no impact of reconstruction algorithms on mean plaque volume or plaque composition (e.g. soft, intermediate and calcified component). However, with increasing ASIR contribution, the percentage of plaque volume component between 401 and 500 HU decreased significantly (p ASIR, which has been developed for noise reduction in latest high resolution CCTA scans, can be used reliably without interfering with the plaque analysis and stenosis severity assessment.

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

NARCIS (Netherlands)

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

2008-01-01

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

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...... was to compare the gene expression of neoangiogenesis and vulnerability-associated genes with 18FDG uptake in patients undergoing carotid endarterectomy. Procedures: Human atherosclerotic carotid artery plaques from symptomatic patients were used for gene expression analysis by quantitative PCR of vascular...... analysis was compared with 18FDG-PET. Results: VEGF and integrin aVß3 gene expression did not correlate with 18FDG uptake, whereas CD34 gene expression exhibited an inverse correlation with 18FDG uptake. Additionally, we established that markers of vulnerability were correlated with 18FDG uptake...

Prevalence of noncalcified coronary plaque in patients with calcium score of 0: the silent enemy.

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Koulaouzidis, George; Charisopoulou, Dafni; Jenkins, Paul J; Koulaouzidis, Anastasios; McArthur, Tony

2013-04-01

Noncalcified coronary artery plaques (NCAPs) are susceptible to rupture, resulting in coronary artery thrombosis. Using computer tomography coronary angiography (CTCA), we evaluated the prevalence and degree of stenosis caused by NCAP in patients without coronary artery calcification (CAC). A retrospective analysis of 447 symptomatic patients with 0 CAC score revealed negative CTCA in 400 (89.5%). Noncalcified coronary artery plaques were demonstrated in 47 (10.5%), with 4 presenting stenosis >50%. Patients with positive CTCA, compared to those with normal CTCA, had significantly higher mean age (56.2 years vs 50.6 years, P < .004) and higher pretest coronary artery disease (CAD) probability (26% vs 34%, P < .0001). Noncalcified coronary artery plaque was predominantly developed in the proximal segment of the left anterior descending artery. Noncalcified coronary artery plaque is present in up to 10% of patients with a CAC score of 0. Computer tomography coronary angiography could be of diagnostic value in symptomatic patients with multiple risk factors for CAD, even in the absence of CAC.

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study.

Science.gov (United States)

Kundel, Vaishnavi; Trivieri, Maria Giovanna; Karakatsanis, Nicolas A; Robson, Phillip M; Mani, Venkatesh; Kizer, Jorge R; Kaplan, Robert; Fayad, Zahi; Shah, Neomi

2018-03-05

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging - hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer-before and after continuous positive airway pressure (CPAP). Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3-6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP. Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBR mean ) and 6.2% (TBR max ) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others). We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

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Long Wang

2018-01-01

Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

Darapladib for preventing ischemic events in stable coronary heart disease

NARCIS (Netherlands)

White, Harvey D.; Held, Claes; Stewart, Ralph; Tarka, Elizabeth; Brown, Rebekkah; Davies, Richard Y.; Budaj, Andrzej; Harrington, Robert A.; Steg, P. Gabriel; Ardissino, Diego; Armstrong, Paul W.; Avezum, Alvaro; Aylward, Philip E.; Bryce, Alfonso; Chen, Hong; Chen, Ming-Fong; Corbalan, Ramon; Dalby, Anthony J.; Danchin, Nicolas; de Winter, Robbert J.; Denchev, Stefan; Diaz, Rafael; Elisaf, Moses; Flather, Marcus D.; Goudev, Assen R.; Granger, Christopher B.; Grinfeld, Liliana; Hochman, Judith S.; Husted, Steen; Kim, Hyo-Soo; Koenig, Wolfgang; Linhart, Ales; Lonn, Eva; López-Sendón, José; Manolis, Athanasios J.; Mohler, Emile R.; Nicolau, José C.; Pais, Prem; Parkhomenko, Alexander; Pedersen, Terje R.; Pella, Daniel; Ramos-Corrales, Marco A.; Ruda, Mikhail; Sereg, Mátyás; Siddique, Saulat; Sinnaeve, Peter; Smith, Peter; Sritara, Piyamitr; Swart, Henk P.; Westendorp, Iris C. D.

2014-01-01

Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated

Data on analysis of coronary atherosclerosis on computed tomography and 18F-sodium fluoride positron emission tomography

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Toshiro Kitagawa

2017-08-01

Full Text Available This article contains the data showing illustrative examples of plaque classification on coronary computed tomography angiography (CCTA and measurement of 18F-sodium fluoride (18F-NaF uptake in coronary atherosclerotic lesions on positron emission tomography (PET. We divided the lesions into one of three plaque types on CCTA (calcified plaque, non-calcified plaque, partially calcified plaque. Focal 18F-NaF uptake of each lesion was quantified using maximum tissue-to-background ratio. This article also provides a representative case with a non-calcified coronary plaque detected on CCTA and identified on 18F-NaF PET/non-contrast computed tomography based on a location of a vessel branch as a landmark. These complement the data reported by Kitagawa et al. (2017 [1].

Rationale and design of the PREDICT (Plaque Registration and Evaluation Detected In Computed Tomography) registry.

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Yamamoto, Hideya; Awai, Kazuo; Kuribayashi, Sachio; Kihara, Yasuki

2014-01-01

At least two-thirds of cases of acute coronary syndrome are caused by disruption of an atherosclerotic plaque. The natural history of individual plaques is unknown and needs to be established. The Plaque Registration and Evaluation Detected In Computed Tomography (PREDICT) registry is a prospective, multicenter, longitudinal, observational registry. This registry was designed to examine the relationships among coronary CT angiography (CTA) findings and clinical findings, mortality, and morbidity. The relationships among progression of coronary atherosclerosis, including changes in plaque characteristics on coronary CTA, and serum lipid levels and modification of coronary risk factors will also be evaluated. From October 2009 to December 2012, 3015 patients who underwent coronary CTA in 29 centers in Japan were enrolled. These patients were followed for 2 years. The primary end points were considered as all-cause mortality and major cardiac events, including cardiac death, nonfatal myocardial infarction, and unstable angina that required hospitalization. The secondary end points were heart failure that required administration of diuretics, target vessel revascularization, cerebral infarction, peripheral arterial disease, and invasive coronary angiography. Blood pressure, serum lipid, and C-reactive protein levels and all cardiovascular events were recorded at 1 and 2 years. If the initial coronary CTA showed any stenosis or plaques, follow-up coronary CTA was scheduled at 2 years to determine changes in coronary lesions, including changes in plaque characteristics. Analysis of the PREDICT registry data will clarify the relationships between coronary CTA findings and cardiovascular mortality and morbidity in a collaborative multicenter fashion. This trial is registered at www.clinicaltrials.gov as NCT 00991835. Copyright © 2014 Society of Cardiovascular Computed Tomography. All rights reserved.

Three-dimensional dynamic contrast-enhanced MRI for the accurate, extensive quantification of microvascular permeability in atherosclerotic plaques

NARCIS (Netherlands)

Calcagno, Claudia; Lobatto, Mark E.; Dyvorne, Hadrien; Robson, Philip M.; Millon, Antoine; Senders, Max L.; Lairez, Olivier; Ramachandran, Sarayu; Coolen, Bram F.; Black, Alexandra; Mulder, Willem J. M.; Fayad, Zahi A.

2015-01-01

Atherosclerotic plaques that cause stroke and myocardial infarction are characterized by increased microvascular permeability and inflammation. Dynamic contrast-enhanced MRI (DCE-MRI) has been proposed as a method to quantify vessel wall microvascular permeability in vivo. Until now, most DCE-MRI

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

A comparative analysis of coronary adventitial T-lymphocytes - an autopsy study

International Nuclear Information System (INIS)

Zubair, A.; Mubarik, A.; Jamal, S.; Naz, S.

2010-01-01

Background: Recent clinical and histopathologic data suggests that inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. The intima has received much attention as a site of inflammation, while the adventitia has remained relatively unexplored. The aim of the present study was to investigate the frequency of inflammatory activity in the cap and shoulder region of un ruptured, atherosclerotic lesions in coronary arteries and to correlate these findings with distribution of inflammatory cells in adventitia. Methods: The study was carried out in Histopathology Department, Army Medical College, Rawalpindi and National University of Sciences and Technology (NUST), from August 2008 to July 2009. Sixty-seven autopsy cases performed at Military Hospital Rawalpindi, Pakistan were selected. The cases were divided into study group and control group. Case group (n=35) included those where cause of death was ischemic heart disease. Those coronary arteries were taken as control (n=32) where atherosclerotic changes were found by chance (death without history of ischemic heart disease). Plaques in each group were assessed by light microscopy and by immunohistochemistry. Results: The ages of the deceased ranged from 38 to 49 years. Within study group, adventitial lymphocytes exhibited strong correlation with erosion, thrombus formation in culprit plaque (p=0.001). No correlation was found between adventitial T-lymphocytes and erosion of plaque (p=0.700) in control group. In 72% of culprit plaques moderate staining for T-lymphocytes was observed in adventitia as well as intima. In control group, most of the cases contained scattered cells. Few cases of stable plaques revealed lymphocytes as clusters, both in adventitia and in intima. Conclusion: Adventitial inflammation may play a pivotal role for atherosclerotic lesion histology and atheroma instability. With the help of these autopsy findings, we hope to be able to reduce the

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

International Nuclear Information System (INIS)

Ma Zhanlong; Teng Gaojun; Mai Xiaoli; Chen Jun; Sun Junhui; Zhang Hongying; Yu Hui; Li Guozhao

2007-01-01

Objective: To evaluate the 1.5 T magnetic resonance imaging system to depict and track in vivo of magnetically labeled endothelial progenitor cells (EPCs), and to study the possibility for preventing the atherosclerotic plaque formation in New Zealand rabbit model of carotid arterial injury after transplantation. Methods: New Zealand rabbit EPCs were isolated, confirmed, expanded and then incubated with home synthesized Fe 2 O 3 -PLL, Prussian blue stain was performed for showing intracellular irons. The model of carotid arterial injury was performed by 2.5F balloons, the group A of 8 rabbits received magnetically labeled EPCs, group B of 3 rabbits received fluorescent-labeled EPCs and the group C of 5 rabbits were given same volume saline injection after endothelial injury of the carotid artery. MR imaging and histology were performed and compared 4 days later for randomly chosen three rabbit, each from one of the three group; all the other rabbits were fed with high lipid diet and examed using MR imaging and histology after 15 weeks. Results: Epcs labeling efficiency was more than 95% by Prussian blue stain, 4 days after transplantation of EPCs, only in group A, the injured endothelium of carotid artery had signal intensity loss in T 2 * WI, which were correlated well with the area where the most Prussian blue staining positive cells were found in histopathology analyses. The rabbits of group A and B which received EPCs transplantation exhibited fewer plaques formation than those of the group C (P 2 O 3 -PLL. The 1.5 T magnetic resonance imaging system could depict and monitor the magnetically labeled endothelial progenitor cells homing to the injured endothelium of the artery, and EPCs contribute to preventing atherosclerotic plaque formation in New Zealand rabbit model of atherosclerosis. (authors)

Circumflex coronary artery with aberrant origin and atherosclerosis

International Nuclear Information System (INIS)

Ozcan, E.; Bozlar, U.; Celik, T.; Tasar, M.

2012-01-01

Full text: Introduction: Circumflex (Cx) coronary artery congenital anomaly is reported to be less than 1% incidence. Coronary arteries with aberrant origin are more likely to have atherosclerosis according to some published literatures. Objectives and tasks: In this study we aim to present computed tomography (CT) angiography findings of a patient, who has Cx artery with aberrant origin and atherosclerotic. Materials and methods: 57-year-old woman without any symptoms who has risk factors to atherosclerosis was referred to our clinic for coronary CT angiography. Results: In CT angiography; we detected Cx coronary artery with aberrant origin (right sinus of valsalva) and retroaortic course. Also we saw intimal irregularities and calcified plaque causing severe narrowing in the proximal segment of artery. Right coronary and left anterior descendant arteries had mild atherosclerosis. Conclusion: Coroner CT angiography, which allows multiplanar imaging with high resolution, is an effective diagnostic tool for coronary artery disease, like not only congenital anomalies but also acquired atherosclerotic disease

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

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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.

Coronary artery atherosclerosis associated with shift work in chemical plant workers by using coronary CT angiography.

Science.gov (United States)

Kang, WonYang; Park, Won-Ju; Jang, Keun-Ho; Kim, Soo-Hyeon; Gwon, Do-Hyeong; Lim, Hyeong-Min; Ahn, Ji-Sung; Moon, Jai-Dong

2016-08-01

The aim of this study was to investigate whether shift work is related to elevated risk of coronary artery disease (CAD) by determining the coronary artery calcium (CAC) score and the presence of coronary artery stenosis by using coronary artery CT angiography (CCTA). In this study, 110 male workers participated and underwent a CCTA examination for CAC scoring, which represents coronary artery plaque, and were evaluated for luminal stenosis. All of the participants were working in the same chemical plant, of whom 70 worked day shifts and 40 worked rotating shifts. In a multivariate logistic regression analysis, including age, smoking status, alcohol consumption, regular exercise and waist circumference, shift work was associated with a 2.89-fold increase in the odds of developing coronary plaque compared with day work (OR, 2.89; 95% CI 1.07 to 7.82). The association between shift work and coronary plaque was strong after adjustment for age, low-density lipoprotein cholesterol, hypertension and diabetes mellitus (OR, 2.92; 95% CI 1.02 to 8.33). In addition, the number of years of shift work employment was associated with coronary plaque. However, no association was found between shift work and coronary artery stenosis. Shift work could induce CAD onset via the atherosclerotic process, and shift work employment duration was associated with an increased risk of atherosclerosis in male workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

NARCIS (Netherlands)

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

2010-01-01

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

Atherosclerotic plaque in the left carotid artery is more vulnerable than in the right.

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Selwaness, Mariana; van den Bouwhuijsen, Quirijn; van Onkelen, Robbert S; Hofman, Albert; Franco, Oscar H; van der Lugt, Aad; Wentzel, Jolanda J; Vernooij, Meike

2014-11-01

Ischemic stroke is more often diagnosed in the left hemisphere than in the right. It is unknown whether this asymmetrical prevalence relates to differences in carotid atherosclerosis. We compared atherosclerotic plaque prevalence, severity, and composition between left and right carotid arteries. In a population-based cohort, carotid MRI scanning was performed in 1414 stroke-free participants (≥45 years). Using a multisequence MRI protocol, we assessed the prevalence, stenosis, and thickness of the plaque and its predominant component (ie, lipid core, intraplaque hemorrhage, calcification, or fibrous tissue in each carotid artery). Differences between left and right side were tested using paired t tests, McNemar test and Generalized Estimating Equation analyses. The majority (85%) of the participants had bilateral carotid plaques. Unilateral plaques were twice more prevalent on the left than on the right side (67% versus 33%; Pthe left (3.1±1.2 versus 2.9±1.3 mm; Pthe left (9.1 versus 5.9%; Pthe right (37.4 versus 31.6% at the left; Pright-sided plaques, which are more calcified and therefore considered more stable. © 2014 American Heart Association, Inc.

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.

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Bonin, L R; Madden, K; Shera, K; Ihle, J; Matthews, C; Aziz, S; Perez-Reyes, N; McDougall, J K; Conroy, S C

1999-03-01

The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2

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...

Relation of ABO Blood Groups to the Plaque Characteristic of Coronary Atherosclerosis.

Science.gov (United States)

Huang, Xingtao; Zou, Yongpeng; Li, Lulu; Chen, Shuyuan; Hou, Jingbo; Yu, Bo

2017-01-01

The ABO blood types related to morphological characteristics of atherosclerosis plaque are not clear. We aimed to evaluate the relationship between ABO blood groups and the coronary plaque characteristic. We retrospectively identified the target lesions in 392 acute coronary syndrome patients who underwent optical coherence tomography examination before stenting. Subjects were divided into different groups according to different blood types. The fibrous cap thickness was significantly thicker in O type compared with non-O type (0.075 ± 0.033 mm versus 0.061 ± 0.024, p blood type groups even between O type and non-O type group ( p > 0.05). The plaques of O type blood group were exhibited more stably compared with non-O type blood group. Moreover, the non-O type blood group have more serious coronary artery stenosis than O type blood group.

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

Science.gov (United States)

Li, Dongye; Wu, Weiheng; Gong, Lei; Li, Yong; Zhang, Qingdui; Zhang, Tao; Zhang, Chao; Zhang, Yu

2015-01-01

Background 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). Methods 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. Results 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 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. PMID:25973795

Noninvasive imaging in the assessment and prevention of coronary heart disease

International Nuclear Information System (INIS)

Llerena Rojas, Luis Roberto; Peix Gonzalez, Amalia; Valiente Mustelier, Juan

2011-01-01

Echocardiography, multidetector computed tomography, magnetic resonance imaging, and nuclear cardiology can all help prevent coronary heart disease. Echocardiography can identify asymptomatic individuals who are at risk of coronary disease and who should receive aggressive preventative therapy by providing data on the carotid intima-media thickness, arterial stiffness and flow-mediated dilatation of the brachial artery. The calcium score is an independent predictor of cardiac events that influences clinical risk scores such as the Framingham risk score. By using multidetector computed tomography or magnetic resonance imaging for coronary angiography, it is possible to visualize both the lumen and vessel walls of coronary arteries and to discriminate between calcified and noncalcified atherosclerotic plaque before invasive coronary angiography is performed. With nuclear cardiology, the functional effects of atherosclerotic lesions can be evaluated by assessing perfusion and ventricular function simultaneously

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.

IL-1β level in Sudanese patients with atherosclerotic coronary heart ...

African Journals Online (AJOL)

McRoy

studies investigating inflammatory cytokines in atherosclerotic patients with coronary heart disease (CHD).[2,5-7]. However, systemic level of IL-1β may still be unreliable marker for atherosclerosis. This is because systemic level of IL-1β could not faithfully reflect the local inflammatory process near the atheromatous lesions.

Predictors of Plaque Rupture Within Nonculprit Fibroatheromas in Patients With Acute Coronary Syndromes: The PROSPECT Study.

Science.gov (United States)

Zheng, Bo; Mintz, Gary S; McPherson, John A; De Bruyne, Bernard; Farhat, Naim Z; Marso, Steven P; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

2015-10-01

The study sought to examine the relative importance of lesion location versus vessel area and plaque burden in predicting plaque rupture within nonculprit fibroatheromas (FAs) in patients with acute coronary syndromes. Previous studies have demonstrated that plaque rupture is associated with larger vessel area and greater plaque burden clustering in the proximal segments of coronary arteries. In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study 3-vessel grayscale and radiofrequency-intravascular ultrasound was performed after successful percutaneous coronary intervention in 697 patients with acute coronary syndromes. Untreated nonculprit lesion FAs were classified as proximal (40 mm) according to the distance from the ostium to the maximum necrotic core site. Overall, 74 ruptured FAs and 2,396 nonruptured FAs were identified in nonculprit vessels. The majority of FAs (73.6%) were located within 40 mm of the ostium, and the vessel area and plaque burden progressively decreased from proximal to distal FA location (both p PROSPECT]; NCT00180466). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Non-obstructive low attenuation coronary plaque predicts three-year acute coronary syndrome events in patients with hypertension. Multidetector computed tomographic study

International Nuclear Information System (INIS)

Nakanishi, Koki; Shimada, Kenei; Fukuda, Shota

2012-01-01

Arterial hypertension is an established risk factor for acute coronary syndrome (ACS). Multidetector computed tomography (MDCT) is an accurate and less invasive technique for assessment of the degree of coronary artery luminal narrowing and characterization of coronary atherosclerosis. We therefore aimed to investigate the predictive power of MDCT for future ACS events and compared with traditional parameters in patients with hypertension. One hundred and thirty-four patients (93 men, mean age 70±11 years) with hypertension underwent MDCT for evaluation of coronary artery disease. MDCT analysis focused on the presence of plaques, the degree of stenosis, and the plaque characteristics. Traditional parameters included Framingham risk score, carotid intima-media thickness, and left ventricular mass index. During a mean follow-up of 39±10 months, ACS events occurred in 10 patients, including myocardial infarction (n=3) and unstable angina (n=7). Multivariate analysis identified total number of low attenuation plaques as an independent predictor of ACS events (p<0.001). We demonstrated that non-obstructive low attenuation coronary plaques on MDCT predicted more accurately future ACS events in patients with hypertension than traditional parameters. (author)

Early detection of premature subclinical coronary atherosclerosis in systemic lupus erythematosus patients

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Khaled Mohamed Said Othman

2013-12-01

Conclusion: Pre-menopausal SLE female patients free from clinical atherosclerotic vascular disease have an increased number of atherosclerotic plaques and CCS, which correlate positively with SLEDAI disease activity score, serum CRP, anticardiolipin antibodies, sICAM-1, E-Selectin, LDL level, total cholesterol level, and cumulative prednisone dose. In addition, we conclude that MDCT is a non-invasive, sensitive, reproducible, and reliable tool for accurate measurement of coronary calcification.

Influence of Adaptive Statistical Iterative Reconstruction on coronary plaque analysis in coronary computed tomography angiography

DEFF Research Database (Denmark)

Precht, Helle; Kitslaar, Pieter H; Broersen, Alexander

2016-01-01

performed. Images were reconstructed using FBP, 30% and 60% adaptive statistical IR (ASIR). Coronary plaque analysis was performed as per patient and per vessel (LM, LAD, CX and RCA) measurements. Lumen and vessel volumes and plaque burden measurements were based on automatic detected contours in each...... reconstruction. Lumen and plaque intensity measurements and HU based plaque characterization were based on corrected contours copied to each reconstruction. RESULTS: No significant changes between FBP and 30% ASIR were found except for lumen- (-2.53 HU) and plaque intensities (-1.28 HU). Between FBP and 60% ASIR...... the change in total volume showed an increase of 0.94%, 4.36% and 2.01% for lumen, plaque and vessel, respectively. The change in total plaque burden between FBP and 60% ASIR was 0.76%. Lumen and plaque intensities decreased between FBP and 60% ASIR with -9.90 HU and -1.97 HU, respectively. The total plaque...

Clinically stable angina pectoris is not necessarily associated with histologically stable atherosclerotic plaques

NARCIS (Netherlands)

van der Wal, A. C.; Becker, A. E.; Koch, K. T.; Piek, J. J.; Teeling, P.; van der Loos, C. M.; David, G. K.

1996-01-01

OBJECTIVE: To investigate the extent of plaque inflammation in culprit lesions of patients with chronic stable angina. DESIGN: Retrospective study. SETTING: Amsterdam reference centre. SUBJECTS: 89 consecutive patients who underwent directional coronary atherectomy, 58 of whom met the following

Coronary Plaque Characteristics Assessed by 256-Slice Coronary CT Angiography and Association with High-Sensitivity C-Reactive Protein in Symptomatic Patients with Type 2 Diabetes

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Jinling Zhang

2016-01-01

Full Text Available Little is known regarding plaque distribution, composition, and the association with inflammation in type 2 diabetes mellitus (DM2. This study aimed to assess the relationship between coronary plaque subtypes and high-sensitivity C-reactive protein levels. Coronary CTA were performed in 98 symptomatic DM2 patients and 107 non-DM2 patients using a 256-slice CT. The extent and types of plaque as well as luminal narrowing were evaluated. Patients with DM2 were more likely to have significant stenosis (>50% with calcified plaques in at least one coronary segment (p<0.01; the prevalence rates of diffuse calcified plaques in the DM2 and non-DM2 groups were 31.6% and 4.7%, respectively (p<0.01. Plasma hs-CRP levels in DM2 with calcified plaques were higher compared with values obtained for the non-DM2 group (p<0.01. In conclusion, combination of coronary CTA and hs-CRP might improve risk stratification in symptomatic DM2 patients.

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

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Dominik von Elverfeldt

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

Cystatin C–Adiponectin Complex in Plasma Associates with Coronary Plaque Instability

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Matsuoka, Tetsuro; Kayama, Kento; Onishi, Sumire; Matsuo, Natsumi

2017-01-01

Aim: Adiponectin (APN) is an adipocyte-derived bioactive molecule with antiatherogenic properties. We previously reported that cystatin C (CysC) abolished the anti-atherogenic effects of APN. We aimed to elucidate the clinical significance of CysC–APN complex in patients with coronary artery disease (CAD). Methods: We enrolled 43 stable CAD male patients to examine the relationship between CysC–APN complex and coronary plaque characteristics. Serum was immunoprecipitated by the anti-APN antibody and immunoblotted by the anti-CysC antibody to demonstrate the presence of CysC–APN complexes in vivo. To confirm their binding in vitro, HEK293T cell lysates overexpressing myc-APN and FLAG-CysC were immunoprecipitated with an anti-myc or anti-FLAG antibody, followed by immunoblotting with an anti-APN or anti-CysC antibody. Results: CysC was identified as a specific co-immunoprecipitant with APN by the anti-APN antibody in human serum. In vitro, FLAG-CysC was co-immunoprecipitated with myc-APN by the antimyc antibody and myc-APN was co-immunoprecipitated with FLAG-CysC by the anti-FLAG antibody. Among CAD patients, serum CysC–APN complex levels negatively correlated with fibrotic components of coronary plaques and positively correlated with either necrotic or lipidic plus necrotic components. Plaque burden negatively correlated with serum APN levels but not serum CysC–APN complex levels. Serum CysC levels had no association with plaque characteristics. In multivariate analysis, CysC–APN complex levels were identified as the strongest negative factor for fibrotic components and the strongest positive factor for both necrotic and lipidic plus necrotic components. Conclusion: Measuring serum CysC–APN complex levels is helpful for evaluating coronary plaque instability in CAD patients. PMID:28321013

Quantitative T1 and T2* carotid atherosclerotic plaque imaging using a three-dimensional multi-echo phase-sensitive inversion recovery sequence: a feasibility study.

Science.gov (United States)

Fujiwara, Yasuhiro; Maruyama, Hirotoshi; Toyomaru, Kanako; Nishizaka, Yuri; Fukamatsu, Masahiro

2018-06-01

Magnetic resonance imaging (MRI) is widely used to detect carotid atherosclerotic plaques. Although it is important to evaluate vulnerable carotid plaques containing lipids and intra-plaque hemorrhages (IPHs) using T 1 -weighted images, the image contrast changes depending on the imaging settings. Moreover, to distinguish between a thrombus and a hemorrhage, it is useful to evaluate the iron content of the plaque using both T 1 -weighted and T 2 *-weighted images. Therefore, a quantitative evaluation of carotid atherosclerotic plaques using T 1 and T 2 * values may be necessary for the accurate evaluation of plaque components. The purpose of this study was to determine whether the multi-echo phase-sensitive inversion recovery (mPSIR) sequence can improve T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of an IPH. T 1 and T 2 * values measured using mPSIR were compared to values from conventional methods in phantom and in vivo studies. In the phantom study, the T 1 and T 2 * values estimated using mPSIR were linearly correlated with those of conventional methods. In the in vivo study, mPSIR demonstrated higher T 1 contrast between the IPH phantom and sternocleidomastoid muscle than the conventional method. Moreover, the T 1 and T 2 * values of the blood vessel wall and sternocleidomastoid muscle estimated using mPSIR were correlated with values measured by conventional methods and with values reported previously. The mPSIR sequence improved T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of the neck region. Although further study is required to evaluate the clinical utility, mPSIR may improve carotid atherosclerotic plaque detection and provide detailed information about plaque components.

Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

Science.gov (United States)

OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

Male Gender and Arterial Hypertension are Plaque Predictors at Coronary Computed Tomography Angiography

Science.gov (United States)

Oliveira, Joselina Luzia Menezes; Hirata, Mario Hiroyuki; Sousa, Amanda Guerra de Moraes Rego; Gabriel, Fabíola Santos; Hirata, Thiago Dominguez Crespo; Tavares, Irlaneide da Silva; Melo, Luiza Dantas; Dória, Fabiana de Santana; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco

2015-01-01

Background Systemic Arterial Hypertension (SAH) is one of the main risk factors for Coronary Artery Disease (CAD), in addition to male gender. Differences in coronary artery lesions between hypertensive and normotensive individuals of both genders at the Coronary Computed Tomography Angiography (CCTA) have not been clearly determined. Objective To Investigate the calcium score (CS), CAD extent and characteristics of coronary plaques at CCTA in men and women with and without SAH. Methods Prospective cross-sectional study of 509 patients undergoing CCTA for CAD diagnosis and risk stratification, from November 2011 to December 2012, at Instituto de Cardiologia Dante Pazzanese. Individuals were stratified according to gender and subdivided according to the presence (HT +) or absence (HT-) of SAH. Results HT+ women were older (62.3 ± 10.2 vs 57.8 ± 12.8, p = 0.01). As for the assessment of CAD extent, the HT+ individuals of both genders had significant CAD, although multivessel disease is more frequent in HT + men. The regression analysis for significant CAD showed that age and male gender were the determinant factors of multivessel disease and CS ≥ 100. Plaque type analysis showed that SAH was a predictive risk factor for partially calcified plaques (OR = 3.9). Conclusion Hypertensive men had multivessel disease more often than women. Male gender was a determinant factor of significant CAD, multivessel disease, CS ≥ 100 and calcified and partially calcified plaques, whereas SAH was predictive of partially calcified plaques. PMID:25861034

CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

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N. V. Pizova

2014-01-01

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

Salusins: Potential Use as a Biomarker for Atherosclerotic Cardiovascular Diseases

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Kengo Sato

2013-01-01

Full Text Available Human salusin-α and salusin-β are related peptides produced from prosalusin. Bolus injection of salusin-β into rats induces more profound hypotension and bradycardia than salusin-α. Central administration of salusin-β increases blood pressure via release of norepinephrine and arginine-vasopressin. Circulating levels of salusin-α and salusin-β are lower in patients with essential hypertension. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs and fibroblasts than salusin-α. Salusin-β accelerates inflammatory responses in human endothelial cells and monocyte-endothelial adhesion. Human macrophage foam cell formation is stimulated by salusin-β but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-deficient mice enhances atherosclerotic lesions; salusin-α infusion reduces lesions. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and salusin-β immunoreactivity have been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Circulating salusin-β levels increase and salusin-α levels decrease in patients with coronary artery disease. These findings suggest that salusin-β and salusin-α may contribute to proatherogenesis and antiatherogenesis, respectively. Increased salusin-β and/or decreased salusin-α levels in circulating blood and vascular tissue are closely linked with atherosclerosis. Salusin-α and salusin-β could be candidate biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases.

HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation.

Science.gov (United States)

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

2015-01-01

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and

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

Science.gov (United States)

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

2016-02-01

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

Intracoronary imaging using attenuation-compensated optical coherence tomography allows better visualisation of coronary artery diseases

Energy Technology Data Exchange (ETDEWEB)

Foin, Nicolas, E-mail: nicolas.foin@gmail.com [International Centre for Circulatory Health, Imperial College London, W2 1LA London (United Kingdom); Mari, Jean Martial [University College London, London (United Kingdom); Nijjer, Sukhjinder; Sen, Sayan; Petraco, Ricardo [International Centre for Circulatory Health, Imperial College London, W2 1LA London (United Kingdom); Ghione, Matteo; Di Mario, Carlo [Biomedical Research Unit, Royal Brompton Hospital, London (United Kingdom); Davies, Justin E. [International Centre for Circulatory Health, Imperial College London, W2 1LA London (United Kingdom); Girard, Michaël J.A. [Department of Bioengineering, National University of Singapore (Singapore); Singapore Eye Research Institute (Singapore)

2013-05-15

Purpose: To allow an accurate diagnosis of coronary artery diseases by enhancing optical coherence tomography (OCT) images of atheromatous plaques using a novel automated attenuation compensation technique. Background: One of the major drawbacks of coronary OCT imaging is the rapid attenuation of the OCT signal, limiting penetration in tissue to only few millimetres. Visualisation of deeper anatomy is however critical for accurate assessment of plaque burden in-vivo. Methods: A compensation algorithm, previously developed to correct for light attenuation in soft tissues and to enhance contrast in ophthalmic OCT images, was applied to intracoronary plaque imaging using spectral-domain OCT. Results: Application of the compensation algorithm significantly increased tissue contrast in the vessel wall and atherosclerotic plaque boundaries. Contrast enhancement allows a better differentiation of plaque morphology, which is particularly important for the identification of lipid rich fibro atheromatous plaques and to guide decision on treatment strategy. Conclusion: The analysis of arterial vessel structure clinically captured with OCT is improved when used in conjunction with automated attenuation compensation. This approach may improve the OCT-based interpretation of coronary plaque morphology in clinical practice.

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.

Coronary CT: clinical indications and future directions; Tomografia de coronarias: indicacoes clinicas e perspectivas futuras

Energy Technology Data Exchange (ETDEWEB)

Nomura, Cesar H.; Serpa, Bruna S.; Kay, Fernando U.; Szarf, Gilberto; Passos, Rodrigo B.; Neto, Roberto S.; Chate, Rodigo C.; Funar, Marcelo B., E-mail: cesarnomura@gmail.com [Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil); Cury, Roberto C. [Hospital Samaritano, Sao Paulo, SP (Brazil)

2011-01-15

Multidetector computed tomography (MDCT) has started its implementation in cardiology with calcium quantification of coronary plaques in the study without contrast, using the calcium score, demonstrating an important independent predictor of future cardiac events. The examination with intravenous contrast, coronary angiography, appeared later as a noninvasive method for evaluation of anatomy and obstructive coronary disease, characterizing the degree of stenosis and the presence of non calcified atherosclerotic plaques, assessing not only the lumen, but also the vessel wall. With the advent of new machines with more detectors and higher temporal resolution has been a reduction in radiation dose and the possibility of new applications. (author)

Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls

KAUST Repository

Hossain, Shaolie S.; Hossainy, Syed F A; Bazilevs, Yuri; Calo, Victor M.; Hughes, Thomas Jr R

2011-01-01

The majority of heart attacks occur when there is a sudden rupture of atherosclerotic plaque, exposing prothrombotic emboli to coronary blood flow, forming clots that can cause blockages of the arterial lumen. Diseased arteries can be treated

CT Determination of Fractional Flow Reserve in Coronary Lesions

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Mester András

2016-12-01

Full Text Available Invasively determined fractional flow reserve (FFR represents the gold-standard method for the functional evaluation of coronary lesions. Coronary computed tomography angiography (CCTA provides characterization of the coronary anatomy, with important morphological information on the atherosclerotic plaques, but does not offer a hemodynamic evaluation of coronary artery lesions. CT evaluation of FFR (FFRCT is a new noninvasive diagnostic method, which provides anatomical and functional assessment of the whole coronary tree, based on computational techniques, with no more radiation or hyperemic agent administration compared with routine CCTA. Recent studies demonstrated the safety and accuracy of FFRCT and its therapeutic use and cost benefits in real-world clinical use.

The relationship of insulin resistance estimated by triglyceride glucose index and coronary plaque characteristics.

Science.gov (United States)

Won, Ki-Bum; Kim, Yun Seok; Lee, Byoung Kwon; Heo, Ran; Han, Donghee; Lee, Ji Hyun; Lee, Sang-Eun; Sung, Ji Min; Cho, Iksung; Park, Hyung-Bok; Cho, In-Jeong; Chang, Hyuk-Jae

2018-05-01

The triglyceride glucose (TyG) index is a useful surrogate marker for insulin resistance, which is an important risk factor for coronary artery disease (CAD). However, data on the relationship of the TyG index and coronary plaque characteristics are limited.This study included 2840 participants with near-normal renal function who underwent coronary computed tomography angiography. CAD was defined as the presence of any plaques, and obstructive CAD was defined as the presence of plaques with ≥50% stenosis. The relationship between the TyG index and noncalcified plaque (NCP), calcified or mixed plaque (CMP), and coronary artery calcium score (CACS) was evaluated.All participants were stratified into 4 groups based on the quartiles of the TyG index. The prevalence of CAD and obstructive CAD significantly increased with increasing quartiles. The risk for NCP and obstructive NCP was not different among all groups. However, compared with group I (lowest quartile), the risk for CMP was higher in groups III (odds ratio [OR]: 1.438) and IV (highest quartile) (OR: 1.895) (P index was associated with an increased risk for CAD (OR: 1.700), obstructive CAD (OR: 1.692), and CACS >400 (OR: 1.448) (P index was independently associated with the presence and severity of CAD due to an increased risk for CMP.

C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques

DEFF Research Database (Denmark)

Pilely, Katrine; Fumagalli, Stefano; Rosbjerg, Anne

2017-01-01

Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are seru...

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

NARCIS (Netherlands)

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

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

Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes.

Science.gov (United States)

Aengevaeren, Vincent L; Mosterd, Arend; Braber, Thijs L; Prakken, Niek H J; Doevendans, Pieter A; Grobbee, Diederick E; Thompson, Paul D; Eijsvogels, Thijs M H; Velthuis, Birgitta K

2017-07-11

-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had a more benign composition of plaques, with fewer mixed plaques and more often only calcified plaques. These observations may explain the increased longevity typical of endurance athletes despite the presence of more coronary atherosclerotic plaque in the most active participants. © 2017 American Heart Association, Inc.

Preintervention lesion remodelling affects operative mechanisms of balloon optimised directional coronary atherectomy procedures: a volumetric study with three dimensional intravascular ultrasound

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von Birgelen, C; Mintz, G; de Vrey, E A; Serruys, P; Kimura, T; Nobuyoshi, M; Popma, J; Leon, M; Erbel, R; de Feyter, P J

2000-01-01

AIMS—To classify atherosclerotic coronary lesions on the basis of adequate or inadequate compensatory vascular enlargement, and to examine changes in lumen, plaque, and vessel volumes during balloon optimised directional coronary atherectomy procedures in relation to the state of adaptive remodelling before the intervention.
DESIGN—29 lesion segments in 29 patients were examined with intravascular ultrasound before and after successful balloon optimised directional coronary atherectomy procedures, and a validated volumetric intravascular ultrasound analysis was performed off-line to assess the atherosclerotic lesion remodelling and changes in plaque and vessel volumes that occurred during the intervention. Based on the intravascular ultrasound data, lesions were classified according to whether there was inadequate (group I) or adequate (group II) compensatory enlargement.
RESULTS—There was no significant difference in patient and lesion characteristics between groups I and II (n = 10 and 19), including lesion length and details of the intervention. Quantitative coronary angiographic data were similar for both groups. However, plaque and vessel volumes were significantly smaller in group I than in II. In group I, 9 (4)% (mean (SD)) of the plaque volume was ablated, while in group II 16 (11)% was ablated (p = 0.01). This difference was reflected in a lower lumen volume gain in group I than in group II (46 (18) mm3 v 80 (49) mm3 (p atherectomy procedures. Plaque ablation was found to be particularly low in lesions with inadequate compensatory vascular enlargement.


Keywords: intravascular ultrasound; ultrasonics; remodelling; coronary artery disease; atherectomy PMID:10648496

Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

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Kovanen, Petri T; Bot, Ilze

2017-12-05

Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

TH-CD-206-12: Image-Based Motion Estimation for Plaque Visualization in Coronary Computed Tomography Angiography

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Zhang, X; Sisniega, A; Zbijewski, W; Stayman, J [Johns Hopkins University, Balitmore, MD (United States); Contijoch, F; McVeigh, E [University of California, San Diego, San Diego, CA (United States)

2016-06-15

Purpose: Visualization and quantification of coronary artery calcification and atherosclerotic plaque benefits from coronary artery motion (CAM) artifact elimination. This work applies a rigid linear motion model to a Volume of Interest (VoI) for estimating motion estimation and compensation of image degradation in Coronary Computed Tomography Angiography (CCTA). Methods: In both simulation and testbench experiments, translational CAM was generated by displacement of the imaging object (i.e. simulated coronary artery and explanted human heart) by ∼8 mm, approximating the motion of a main coronary branch. Rotation was assumed to be negligible. A motion degraded region containing a calcification was selected as the VoI. Local residual motion was assumed to be rigid and linear over the acquisition window, simulating motion observed during diastasis. The (negative) magnitude of the image gradient of the reconstructed VoI was chosen as the motion estimation objective and was minimized with Covariance Matrix Adaptation Evolution Strategy (CMAES). Results: Reconstruction incorporated the estimated CAM yielded signification recovery of fine calcification structures as well as reduced motion artifacts within the selected local region. The compensated reconstruction was further evaluated using two image similarity metrics, the structural similarity index (SSIM) and Root Mean Square Error (RMSE). At the calcification site, the compensated data achieved a 3% increase in SSIM and a 91.2% decrease in RMSE in comparison with the uncompensated reconstruction. Conclusion: Results demonstrate the feasibility of our image-based motion estimation method exploiting a local rigid linear model for CAM compensation. The method shows promising preliminary results for the application of such estimation in CCTA. Further work will involve motion estimation of complex motion corrupted patient data acquired from clinical CT scanner.

Subclinical Coronary Plaque Burden in Asymptomatic Relatives of Patients With Documented Premature Coronary Artery Disease

DEFF Research Database (Denmark)

Christiansen, Morten Krogh; Jensen, Jesper Møller; Bøtker, Hans Erik

Introduction: A family history of premature coronary artery disease (CAD) is a well-known risk factor for adverse coronary events with age of onset being inversely related to the degree of heritability. Hypothesis: We hypothesized that asymptomatic first degree relatives, of patients with premature...... CAD, suffer a high burden of subclinical coronary atherosclerosis. Methods: First degree relatives, aged 30-65 years, of patients with a documented coronary revascularization procedure before the age of 40 years, were invited to participate in the study. Participants were matched by age, sex...... and absence of a family history, with patients referred for coronary CT angiography (CTA) because of atypical angina or non-anginal chest pain. A pooled blinded analysis was performed. The main outcome measure was the number of plaque-affected coronary segments. Results: 88 relatives and 88 symptomatic...

Clinical outcome of nonculprit plaque ruptures in patients with acute coronary syndrome in the PROSPECT study.

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Xie, Yong; Mintz, Gary S; Yang, Junqing; Doi, Hiroshi; Iñiguez, Andrés; Dangas, George D; Serruys, Patrick W; McPherson, John A; Wennerblom, Bertil; Xu, Ke; Weisz, Giora; Stone, Gregg W; Maehara, Akiko

2014-04-01

The aim of this study was to report the frequency, patient and lesion-related characteristics, and outcomes of subclinical, nonculprit plaque ruptures in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Plaque rupture and subsequent thrombosis is the most common cause of acute coronary syndrome (ACS). Secondary, subclinical, nonculprit plaque ruptures have been seen in both stable patients and patients with ACS; however, reports of the natural history of these secondary plaque ruptures are limited. After successful stenting in 697 patients with ACS, 3-vessel grayscale and intravascular ultrasound virtual histology (IVUS-VH) was performed in the proximal-mid segments of all 3 coronary arteries as part of a prospective multicenter study. Among 660 patients with complete IVUS data, 128 plaque ruptures were identified in 105 nonculprit lesions in 100 arteries from 93 patients (14.1%). Although the minimum lumen area (MLA) was similar, the plaque burden was significantly greater in nonculprit lesions with a plaque rupture compared with nonculprit lesions without a plaque rupture (66.0% [95% confidence interval: 64.5% to 67.4%] vs. 56.0% [95% confidence interval: 55.6% to 56.4%]; p PROSPECT]; NCT00180466). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Relationship between aortic valve calcification and the severity of coronary atherosclerotic disease.

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Qian, Juying; Chen, Zhangwei; Ge, Junbo; Ma, Jianying; Chang, Shufu; Fan, Bing; Liu, Xuebo; Ge, Lei

2010-07-01

Aortic valve calcification (AVC), which has been confirmed to be associated with various risk factors of cardiac disease, is common in the elderly and associated with increased cardiovascular mortality. It has been hypothesized that AVC is associated with coronary atherosclerotic disease, and its severity. Between July 2007 and November 2007, a total of 235 patients with chest pain or chest distress were admitted to the authors' institution for coronary angiography. The severity of coronary atherosclerotic disease (CAD) was evaluated by the Gensini score, the number of stenosed vessels, and the prevalence of total occlusion. All patients underwent transthoracic echocardiography to detect AVC. Patients with CAD had a higher prevalence of AVC than those without CAD (44% versus 26%, p = 0.005). Likewise, the prevalence of AVC was significantly higher in patients with a higher Gensini score than in those with a lower score. Patients with AVC had a higher prevalence of CAD, and higher Gensini scores and numbers of stenosed coronary arteries, even after stratification by age (65 years). On multivariable logistic regression analysis for CAD, the odds ratio (OR) of AVC was 2.315 (95% confidence interval (CI): 1.158-4.629, p = 0.018); this value was higher than that for total cholesterol (OR = 1.637, p = 0.008), lipoprotein-a (OR = 1.003, p = 0.015) and fibrinogen (OR = 1.009, p = 0.006), and marginally less than that for male gender (OR = 2.665, p = 0.005). Patients with AVC had a higher prevalence and greater severity of CAD.

High titer of anti-citrullinated peptide antibody is a risk factor for severe carotid atherosclerotic plaque in patients with rheumatoid arthritis: the TOMORROW study.

Science.gov (United States)

Okano, Tadashi; Inui, Kentaro; Sugioka, Yuko; Sugioka, Kenichi; Matsumura, Yoshiki; Takahashi, Shinji; Tada, Masahiro; Mamoto, Kenji; Wakitani, Shigeyuki; Koike, Tatsuya; Nakamura, Hiroaki

2017-08-01

Cardiovascular disease is one of the complications of rheumatoid arthritis (RA). We researched the morbidity and severity of existing carotid atherosclerosis plaque and associated risk factors in patients with RA. This study included 413 participants, including 208 patients with RA and 205 age- and sex-matched healthy volunteers. Carotid ultrasound, clinical data collection and assessment of cardiovascular risk factors were performed. Atherosclerotic plaque was defined as an intima-media thickness ≥ 1.1 mm. Severity of plaque was assessed by plaque score, defined as the sum of the maximal thickness of all plaques in bilateral carotid arteries. Data were analyzed from 200 patients with RA and 202 controls. Carotid plaque was observed more frequently in patients with RA than controls (47.0 vs. 36.1%, P = 0.027). Moreover, plaque score was significantly higher in RA patients (P = 0.032). In logistic regression analysis, RA represented an independent risk factor for the presence of plaque (adjusted odds ratio, 1.68; 95% confidence interval, 1.03-2.74). Comparing RA patients with and without plaque, anti-cyclic citrullinated peptide (anti-CCP) antibodies titer was significantly higher in patients with plaque (315.8 ± 454.1 U/mL) than in patients without (165.7 ± 281.1 U/mL; P = 0.005). Moreover, multiple linear regression analysis clarified that anti-CCP antibody titer was associated with plaque score in patients with RA. High prevalence of any carotid plaques and severe carotid plaques were more frequent in patients with RA. High titer of anti-CCP antibodies represented a risk factor for severe carotid atherosclerotic plaque in patients with RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Peeled Guidewire Coating with Debulked Plaque Obtained by Directional Coronary Atherectomy

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Rikuta Hamaya

2017-01-01

Full Text Available Percutaneous directional coronary atherectomy (DCA is a plaque debulking method performed in Japan, and recently a renewed DCA device has been launched. We present a case with a tight left anterior descending lesion undergoing percutaneous coronary intervention with application of DCA. After several sessions of DCA, white plaques accompanied by green, stringed materials were obtained from the device; some materials were considerably long (approximately 15 mm in length. A drug-eluting stent was subsequently implanted, and the procedure was completed successfully without any complications. The extracted plaques and artificial materials were pathologically examined, and no inflammatory changes were detected on plaques adjacent to the material. Assessing pathological findings and structure of the DCA catheter, the obtained artificial materials were considered as peeled guidewire, possibly resulting from the friction between the guidewire and metallic bearing in the housing of DCA catheter. Of note, this phenomenon has been recognized even in other DCA cases in which guidewires of the other kind are used. We report this phenomenon for the first time, warning of theoretically possible distal embolization of artificial materials caused by any debulking devices.

Associations between Tobacco, Alcohol, and Drug Use with Coronary Artery Plaque among HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study.

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Sean G Kelly

Full Text Available We characterized associations between smoking, alcohol, and recreational drug use and coronary plaque by HIV serostatus within the Multicenter AIDS Cohort Study (MACS.MACS participants (N = 1005, 621 HIV+ and 384 HIV- underwent non-contrast CT scanning to measure coronary artery calcium; 764 underwent coronary CT angiograms to evaluate plaque type and extent. Self-reported use of alcohol, tobacco, smoked/inhaled cocaine, methamphetamine, ecstasy, marijuana, inhaled nitrites, and erectile dysfunction drugs was obtained at semi-annual visits beginning 10 years prior to CT scanning. Multivariable logistic and linear regression models were performed, stratified by HIV serostatus.Among HIV+ men, current smoking, former smoking, and cumulative pack years of smoking were positively associated with multiple coronary plaque measures (coronary artery calcium presence and extent, total plaque presence and extent, calcified plaque presence, and stenosis >50%. Smoking was significantly associated with fewer plaque measures of comparable effect size among HIV- men; current smoking and calcified plaque extent was the only such association. Heavy alcohol use (>14 drinks/week was associated with stenosis >50% among HIV+ men. Among HIV- men, low/moderate (1-14 drinks/week and heavy alcohol use were inversely associated with coronary artery calcium and calcified plaque extent. Few significant associations between other recreational drug use and plaque measures were observed.Smoking is strongly associated with coronary plaque among HIV+ men, underscoring the value of smoking cessation for HIV+ persons. Alcohol use may protect against coronary artery calcium and calcified plaque progression in HIV- (but not HIV+ men. Few positive associations were observed between recreational drug use and coronary plaque measures.

Risk assessment of atherosclerotic plaques based on global biomechanics.

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

2013-09-01

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

NF-κB inhibitors that prevent foam cell formation and atherosclerotic plaque accumulation.

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Plotkin, Jesse D; Elias, Michael G; Dellinger, Anthony L; Kepley, Christopher L

2017-08-01

The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology.Lipoprotein-induced generation of TNF-α, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to be mediated through the NF-κB pathway as FD reduced expression of NF-κB and atherosclerosis-associated genes. Compared to controls, FD dramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Optical Coherence Tomography Analysis of Attenuated Plaques Detected by Intravascular Ultrasound in Patients with Acute Coronary Syndromes

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Takashi Kubo

2011-01-01

Full Text Available Background. Recent intravascular ultrasound (IVUS studies have demonstrated that hypoechoic plaque with deep ultrasound attenuation despite absence of bright calcium is common in acute coronary syndrome. Such “attenuated plaque” may be an IVUS characteristic of unstable lesion. Methods. We used optical coherence tomography (OCT in 104 patients with unstable angina to compare lesion characteristics between IVUS-detected attenuated plaque and nonattenuated plaque. Results. IVUS-detected attenuated plaque was observed in 41 (39% patients. OCT-detected lipidic plaque (88% versus 49%, <0.001, thin-cap fibroatheroma (48% versus 16%, <0.001, plaque rupture (44% versus 11%, <0.001, and intracoronary thrombus (54% versus 17%, <0.001 were more often seen in IVUS-detected attenuated plaques compared with nonattenuated plaques. Conclusions. IVUS-detected attenuated plaque has many characteristics of unstable coronary lesion. The presence of attended plaque might be an important marker of lesion instability.

The values of wall shear stress, turbulence kinetic energy and blood pressure gradient are associated with atherosclerotic plaque erosion in rabbits.

Science.gov (United States)

Sameshima, Naoki; Yamashita, Atsushi; Sato, Shinya; Matsuda, Shuntaro; Matsuura, Yunosuke; Asada, Yujiro

2014-01-01

To clarify the contribution of hemodynamic factors to the onset of plaque erosion in smooth muscle cell (SMC)-rich atherosclerotic plaque. We developed a rabbit model of SMC-rich atherosclerotic plaque with various degree of stenosis induced by incomplete ligation and generated three-dimensional models of five rabbit femoral arteries based on 130-162 serial histological cross-sections at 100-μm intervals per artery. We performed a computational blood flow simulation using the Reynolds-averaged Navier-Stokes model and calculated the wall shear stress (WSS), turbulence kinetic energy (TKE), blood pressure (BP) and blood pressure gradients (BPG) in eight sections (the inlet, the stenotic portion and areas 1, 2 and 5mm from the stenotic portion) in each rabbit. We also investigated whether the magnitude of WSS or TKE was related to the presence or absence of erosive injury by evaluating six points (the locally highest, median and lowest of WSS or TKE) in each section. The magnitudes of WSS, TKE and BPG, but not BP, correlated significantly with the extent of histologically-defined plaque erosion (WSS, r=0.55, p＜0.001; TKE, r=0.53, p＜0.001; BPG, r=0.61, p＜0.0001, n=40). The values for WSS and TKE were significantly larger at sites with, compared to without, erosive injury (n=107 and n=119 points, respectively; both p＜0.0001). These results suggest that increased values of WSS, TKE and BPG considerably contribute to the onset of plaque erosion.

Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus.

Science.gov (United States)

Hall, Leangelo N; Sanchez, Laura R; Hubbard, Jane; Lee, Hang; Looby, Sara E; Srinivasa, Suman; Zanni, Markella V; Stanley, Takara L; Lo, Janet; Grinspoon, Steven K; Fitch, Kathleen V

2017-01-01

Dietary sweeteners may contribute to metabolic dysregulation and cardiovascular disease (CVD), but this has not been assessed in human immunodeficiency virus (HIV). One hundred twenty-four HIV-infected and 56 non-HIV-infected participants, without history of known coronary artery disease were included. Dietary intake was assessed using a 4-day food record. Coronary plaque was determined using cardiac computed tomography angiography. Human immunodeficiency virus-infected participants had significantly greater intake of dietary sweeteners, including total sugar ( P = .03) and added sugar ( P = .009); intake of aspartame (artificial sweetener) was greater among aspartame consumers with HIV versus non-HIV consumers ( P = .03). Among HIV-infected participants, aspartame intake was significantly associated with coronary plaque ( P = .002) and noncalcified plaque ( P = .007) segments, as well as markers of inflammation/immune activation (monocyte chemoattractant protein 1 and lipoprotein-associated phospholipase A 2 ), which may contribute to increased atherogenesis. In multivariable regression modeling, aspartame remained an independent predictor of plaque in HIV. In contrast, among non-HIV-infected participants, no sweetener type was shown to relate to plaque characteristics. We demonstrate increased intake of dietary sweeteners and a potential novel association between aspartame intake, plaque burden, and inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk in HIV. Further studies should address potential mechanisms by which aspartame may contribute to increased plaque burden and cardiovascular benefits of dietary strategies targeting aspartame intake in HIV. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Prognostic implications of nonobstructive coronary plaques in patients with non-ST-segment elevation myocardial infarction: a multidetector computed tomography study

DEFF Research Database (Denmark)

Kristensen, Thomas S; Kofoed, Klaus F; Kühl, Jørgen T

2011-01-01

We sought to determine whether the amount of noncalcified plaque (NCP) in nonobstructive coronary lesions as detected by multidetector computed tomography (MDCT) was a predictor of future coronary events.......We sought to determine whether the amount of noncalcified plaque (NCP) in nonobstructive coronary lesions as detected by multidetector computed tomography (MDCT) was a predictor of future coronary events....

Matrix metalloproteinases in acute coronary syndromes: current perspectives.

Science.gov (United States)

Kampoli, Anna-Maria; Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Androulakis, Emmanuel; Tsiamis, Eleftherios; Latsios, George; Stefanadis, Christodoulos

2012-01-01

Matrix metalloproteinases (MMPs) are a family of zinc metallo-endopeptidases secreted by cells and are responsible for much of the turnover of matrix components. Several studies have shown that MMPs are involved in all stages of the atherosclerotic process, from the initial lesion to plaque rupture. Recent evidence suggests that MMP activity may facilitate atherosclerosis, plaque destabilization, and platelet aggregation. In the heart, matrix metalloproteinases participate in vascular remodeling, plaque instability, and ventricular remodelling after cardiac injury. The aim of the present article is to review the structure, function, regulation of MMPs and to discuss their potential role in the pathogenesis of acute coronary syndromes, as well as their contribution and usefullness in the setting of the disease.

Myocardial perfusion scintigraphy fi ndings in patients with mild coronary atherosclerotic lesions on coronary angiography

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Zeki Dostbil

2010-09-01

Full Text Available Objectives: Myocardial perfusion scintigraphy (MPS iswidely used in functional assessment of myocardial per-fusion. But, some study results are in contradiction withseverity of coronary artery disease detected by coronaryangiography (CA. It is frequently encountered case thatCA is completely normal whereas MPS describes isch-emia. In this study, we aimed to investigate whether mildatherosclerotic lesions cause ischemia.Materials and methods: MPS with 99mTc-MIBI was per-formed in 52 patients who applied to cardiology clinics forhistory of chest pain and underwent diagnostic CA within3 months.Results: In 22 of 52 patients with mild atherosclerotic le-sions, ischemia in various degrees was detected on MPS.In statistical analysis, any signifi cant relationship was notfound between ischemia and gender, hypertension, DM,dyslipidemia, smoking, mitral valve insuffi ciency, left ven-tricular hypertrophy, exercise testing result and affectedcoronary artery.Conclusion: Our study fi ndings have shown that mild ath-erosclerotic lesions even at very early stage may causemyocardial ischemia

Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics.

Science.gov (United States)

Lee, Joo Myung; Choi, Gilwoo; Koo, Bon-Kwon; Hwang, Doyeon; Park, Jonghanne; Zhang, Jinlong; Kim, Kyung-Jin; Tong, Yaliang; Kim, Hyun Jin; Grady, Leo; Doh, Joon-Hyung; Nam, Chang-Wook; Shin, Eun-Seok; Cho, Young-Seok; Choi, Su-Yeon; Chun, Eun Ju; Choi, Jin-Ho; Nørgaard, Bjarne L; Christiansen, Evald H; Niemen, Koen; Otake, Hiromasa; Penicka, Martin; de Bruyne, Bernard; Kubo, Takashi; Akasaka, Takashi; Narula, Jagat; Douglas, Pamela S; Taylor, Charles A; Kim, Hyo-Soo

2018-03-14

We investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS). ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known. Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR CT ], change in FFR CT across the lesion [△FFR CT ], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR CT , △FFR CT , WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC). The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p stress than nonculprit lesions (all p values statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001). Noninvasive hemodynamic assessment enhanced

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

DEFF Research Database (Denmark)

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

2017-01-01

chimeras of eGFP+Apoe-/- and Apoe-/- mouse embryos and in mice with a mosaic expression of fluorescent proteins in medial SMCs that were rendered atherosclerotic by PCSK9-induced hypercholesterolemia. Fibrous caps in aggregation chimeras were found constructed from large, endothelial-aligned layers...... in the cap and heterogeneous ACTA2- SMCs in the plaque interior, including chondrocyte-like cells and cells with intracellular lipid and crystalline material. Fibrous cap SMCs were invariably arranged in endothelium-aligned clonal sheets, confirming results in the aggregation chimeras. Analysis of the clonal...

Clinical and angiographic characteristics of patients likely to have vulnerable plaques: analysis from the PROSPECT study.

Science.gov (United States)

Bourantas, Christos V; Garcia-Garcia, Hector M; Farooq, Vasim; Maehara, Akiko; Xu, Ke; Généreux, Philippe; Diletti, Roberto; Muramatsu, Takashi; Fahy, Martin; Weisz, Giora; Stone, Gregg W; Serruys, Patrick W

2013-12-01

This study sought to determine the clinical and angiographic variables that would identify patients with high-risk "vulnerable" coronary plaques. In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, in patients successfully treated for acute coronary syndrome (ACS), plaque composition, plaque burden, and minimal luminal area as detected by 3-vessel radiofrequency intravascular ultrasound (IVUS) imaging were associated with an increased risk of developing future events from untreated atherosclerotic lesions (vulnerable plaques). Whether baseline demographic and angiographic findings can be used to identify patients most likely to have vulnerable coronary plaques has not been examined. On the basis of 3-vessel radiofrequency IVUS imaging, patents in the PROSPECT trial were classified in 2 groups according to whether or not one or more untreated high-risk plaques were present, defined as having ≥2 high-risk features (a thin-cap fibroatheroma, plaque burden ≥70%, and/or minimal luminal area ≤4 mm(2)). The high-risk group (those with one or more high-risk lesions) had higher Framingham risk score (7.5 ± 3.4 vs. 6.9 ± 3.3; p = 0.04), more extensive coronary artery disease, and more nonculprit lesion-related cardiovascular events during the 3-year follow-up (hazard ratio: 2.63; 95% confidence interval: 1.62 to 3.66; p < 0.0001). However, demographic factors had poor discrimination in detecting high-risk patients (area under the curve 0.55), and discrimination was only slightly improved when angiographic variables were entered into the model (area under the curve 0.64). Clinical and angiographic characteristics had poor predictive accuracy in identifying patients with untreated high-risk plaques related to future adverse events. This finding highlights the potential value of comprehensive 3-vessel imaging assessment (either invasive or noninvasive) to evaluate plaque phenotype for more accurate risk

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

OpenAIRE

M Djalali; SR A Hoseiny; F Siassi; N Fardad; R Ghiasvand; TR Neyestani

2007-01-01

Background: Increased level of serum homocysteine is one of the risk factor of atherosclerosis. Its production related in some sulfur amino acids such as methionine. Some important cofactors that are involved in metabolic pathways of this amino acid are folate and vitamin B12. We have assessed the status of methionine, folic acid, and vitamin B12 in some coronary atherosclerotic male patients.Methods: In this case-control study, 46 cases of coronary atherosclerosis were selected from male pat...

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

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Dheeraj eKhurana

2013-04-01

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

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

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Qing Sun

2014-07-01

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

Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study.

Science.gov (United States)

Lerman, Joseph B; Joshi, Aditya A; Chaturvedi, Abhishek; Aberra, Tsion M; Dey, Amit K; Rodante, Justin A; Salahuddin, Taufiq; Chung, Jonathan H; Rana, Anshuma; Teague, Heather L; Wu, Jashin J; Playford, Martin P; Lockshin, Benjamin A; Chen, Marcus Y; Sandfort, Veit; Bluemke, David A; Mehta, Nehal N

2017-07-18

Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25). Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy. Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32, P =0.02) and similar HRP prevalence ( P =0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22, P =0.001), NCB (1.18±0.33 versus 1.03±0.21, P =0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1-31.7; P =0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (β=0.45, 0.23-0.67; P psoriasis had greater NCB and increased HRP prevalence than

Differential impact of five coronary devices on plaque size: insights from the ABSORB and SPIRIT trials.

Science.gov (United States)

García-García, Héctor M; Serruys, Patrick W; Campos, Carlos M; Onuma, Yoshinobu

2014-08-20

Coronary plaque size modification, by either local (device) or systemic treatments, has been the target for many years. From ABSORB Cohort A (Absorb BVS 1.0), ABSORB Cohort B (Absorb BVS 1.1), SPIRIT FIRST (Multi-Link Vision vs. Xience V) & SPIRIT II (Xience V vs. Taxus), we calculated the total plaque area (vessel minus lumen area - thus it comprises both compartments - the plaque behind struts and the neointima.) changes by IVUS. A total of 313 patients were included. Comparison-at-6-month follow-up: All devices induced an increase in the total plaque area. The largest increase occurred with Vision and Taxus stents as compared to other devices [Absorb BVS (1.0 and 1.1) and Xience V], (p=0.0002). Comparison-at-2-year follow-up: Absorb BVS 1.1 had a larger increase from post procedure in total plaque compared to Absorb BVS 1.0, Xience V and Taxus (p=0.0499). However, in Absorb BVS 1.1 total plaque showed a reduction of 2.2% from 1 to 3 years. Specifically, the total plaque in the sequential cohorts of Absorb BVS 1.1 increased 16.2% from baseline to 2 years (Cohort B1) while at 3 years this increase is only 5% compared to baseline (Cohort B2). Local devices affect coronary plaque size differently and it depends on the platform (metallic vs. polymeric) and on whether it is a bare - or drug eluting stent. Coronary scaffolds appear to be a promising alternative to metallic stents since they allow plaque regression at long-term follow-up. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Exclusion of Atherosclerotic Plaque from the Circulation Using Stent-Grafts: Alternative to Carotid Stenting with a Protection Device?

International Nuclear Information System (INIS)

Peynircioglu, Bora; Geyik, Serdar; Yavuz, Kivilcim; Cil, Barbaros E.; Saatci, Isil; Cekirge, Saruhan

2007-01-01

Purpose. To retrospectively assess the feasibility, safety, and clinical mid-term outcome of patients undergoing carotid artery stenting with stent-grafts. Methods. Over a 4 year period stent-grafts were used in the endovascular treatment of symptomatic internal carotid artery stenosis in 12 patients (2 women, 10 men, aged 47-83 (mean 64) years). Protection devices were not used. Possible microembolic complications were evaluated by magnetic resonance imaging (MRI) examinations of the brain before and the day after the procedure in all patients. Mean follow-up was 22 months (range 1-42 months), by Doppler ultrasonography and conventional angiography as well as clinical examination .Results. The technical success rate was 100%. A total of 13 coronary stent-grafts were used. The mean stenosis rate (in terms of diameter) was 85% and the mean length of stent-grafts used was 20.9 mm. The mean diameter to which the stent-grafts were dilated was 4.66 mm. In-hospital complications occurred in 1 patient who suffered a minor femoral access hematoma that did not require transfusion or surgical decompression. Post-stenting diffusion-weighted MRI revealed several ipsilateral silent microemboli in only 1 case, which was completely asymptomatic. Two patients had a major stroke after 2 years of follow-up. Restenosis was found in 2 patients who underwent successful balloon dilatation followed by placement of a self-expandable bare stent within the stent-grafts. Conclusions. Stent-grafts may prevent microembolic complications during stenting of atherosclerotic carotid lesions in selected cases, offering immediate exclusion of the atherosclerotic lesion from the circulation by pressing the plaque against the vessel wall. Comparative, randomized studies in larger series of patients are needed with carotid-dedicated stent-graft designs

Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE-/- mice

International Nuclear Information System (INIS)

Campen, Matthew J.; Lund, Amie K.; Knuckles, Travis L.; Conklin, Daniel J.; Bishop, Barbara; Young, David; Seilkop, Steven; Seagrave, JeanClare; Reed, Matthew D.; McDonald, Jacob D.

2010-01-01

Recent epidemiological studies suggest that traffic-related air pollution may have detrimental effects on cardiovascular health. Previous studies reveal that gasoline emissions can induce several enzyme pathways involved in the formation and development of atherosclerotic plaques. As a direct comparison, the present study examined the impact of diesel engine emissions on these pathways, and further examined the effects on vascular lesion pathology. Apolipoprotein E-null mice were simultaneously placed on a high-fat chow diet and exposed to four concentrations, plus a high concentration exposure with particulates (PM) removed by filtration, of diesel emissions for 6 h/day for 50 days. Aortas were subsequently assayed for alterations in matrix metalloproteinase-9, endothelin-1, and several other biomarkers. Diesel induced dose-related alterations in gene markers of vascular remodeling and aortic lipid peroxidation; filtration of PM did not significantly alter these vascular responses, indicating that the gaseous portion of the exhaust was a principal driver. Immunohistochemical analysis of aortic leaflet sections revealed no net increase in lesion area, but a significant decrease in lipid-rich regions and increasing trends in macrophage accumulation and collagen content, suggesting that plaques were advanced to a more fragile, potentially more vulnerable state by diesel exhaust exposure. Combined with previous studies, these results indicate that whole emissions from mobile sources may have a significant role in promoting chronic vascular disease.

PCA-based polling strategy in machine learning framework for coronary artery disease risk assessment in intravascular ultrasound: A link between carotid and coronary grayscale plaque morphology.

Science.gov (United States)

Araki, Tadashi; Ikeda, Nobutaka; Shukla, Devarshi; Jain, Pankaj K; Londhe, Narendra D; Shrivastava, Vimal K; Banchhor, Sumit K; Saba, Luca; Nicolaides, Andrew; Shafique, Shoaib; Laird, John R; Suri, Jasjit S

2016-05-01

Percutaneous coronary interventional procedures need advance planning prior to stenting or an endarterectomy. Cardiologists use intravascular ultrasound (IVUS) for screening, risk assessment and stratification of coronary artery disease (CAD). We hypothesize that plaque components are vulnerable to rupture due to plaque progression. Currently, there are no standard grayscale IVUS tools for risk assessment of plaque rupture. This paper presents a novel strategy for risk stratification based on plaque morphology embedded with principal component analysis (PCA) for plaque feature dimensionality reduction and dominant feature selection technique. The risk assessment utilizes 56 grayscale coronary features in a machine learning framework while linking information from carotid and coronary plaque burdens due to their common genetic makeup. This system consists of a machine learning paradigm which uses a support vector machine (SVM) combined with PCA for optimal and dominant coronary artery morphological feature extraction. Carotid artery proven intima-media thickness (cIMT) biomarker is adapted as a gold standard during the training phase of the machine learning system. For the performance evaluation, K-fold cross validation protocol is adapted with 20 trials per fold. For choosing the dominant features out of the 56 grayscale features, a polling strategy of PCA is adapted where the original value of the features is unaltered. Different protocols are designed for establishing the stability and reliability criteria of the coronary risk assessment system (cRAS). Using the PCA-based machine learning paradigm and cross-validation protocol, a classification accuracy of 98.43% (AUC 0.98) with K=10 folds using an SVM radial basis function (RBF) kernel was achieved. A reliability index of 97.32% and machine learning stability criteria of 5% were met for the cRAS. This is the first Computer aided design (CADx) system of its kind that is able to demonstrate the ability of coronary

Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls

KAUST Repository

Hossain, Shaolie S.

2011-08-20

The majority of heart attacks occur when there is a sudden rupture of atherosclerotic plaque, exposing prothrombotic emboli to coronary blood flow, forming clots that can cause blockages of the arterial lumen. Diseased arteries can be treated with drugs delivered locally to vulnerable plaques. The objective of this work was to develop a computational tool-set to support the design and analysis of a catheter-based nanoparticulate drug delivery system to treat vulnerable plaques and diffuse atherosclerosis. A threedimensional mathematical model of coupled mass transport of drug and drug-encapsulated nanoparticles was developed and solved numerically utilizing isogeometric finite element analysis. Simulations were run on a patient-specific multilayered coronary artery wall segment with a vulnerable plaque and the effect of artery and plaque inhomogeneity was analyzed. The method captured trends observed in local drug delivery and demonstrated potential for optimizing drug design parameters, including delivery location, nanoparticle surface properties, and drug release rate. © Springer-Verlag 2011.

Coronary Plaque Volume and Composition Assessed by Computed Tomography Angiography in Patients With Late-Onset Major Depression

DEFF Research Database (Denmark)

Devantier, Torben Albert; Nørgaard, Bjarne Linde; Ovrehus, Kristian Altern

2013-01-01

Background: Depression is a stronger predictor for the onset of or death from clinical coronary artery disease than traditional cardiovascular risk factors. The association between depression and coronary artery disease has previously been investigated in non-contrast enhanced computed tomography...... studies with conflicting results. The aim of this study was to further elucidate the depression-coronary artery disease relation by use of coronary computed tomography angiography. Methods: The calcified and noncalcified coronary plaque volumes were determined by semiautomatic volumetric quantification...... with controls (14% vs. 7%, p = 0.044). Correspondingly, having depression was associated with an increased calcified plaque proportion of 11.3 [95% confidence interval: 2.63-20.1; p = 0.012] percentage points after adjustment for demographics and cardiovascular risk factors. Conclusion: The proportion...

Acute non-atherosclerotic ST-segment elevation myocardial infarction in an adolescent with concurrent hemoglobin H-Constant Spring disease and polycythemia vera

Directory of Open Access Journals (Sweden)

Ekarat Rattarittamrong

2015-09-01

Full Text Available Thrombosis is a major complication of polycythemia vera (PV and also a well-known complication of thalassemia. We reported a case of non-atherosclerotic ST-segment elevation myocardial infarction (STEMI in a 17- year-old man with concurrent post-splenectomized hemoglobin H-Constant Spring disease and JAK2 V617F mutation-positive PV. The patient initially presented with extreme thrombocytosis (platelet counts greater than 1,000,000/μL and three months later developed an acute STEMI. Coronary artery angiography revealed an acute clot in the right coronary artery without atherosclerotic plaque. He was treated with plateletpheresis, hydroxyurea and antiplatelet agents. The platelet count decreased and his symptoms improved. This case represents the importance of early diagnosis, awareness of the increased risk for thrombotic complications, and early treatment of PV in patients who have underlying thalassemia with marked thrombocytosis.

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

Assessment of atherosclerotic luminal narrowing of coronary arteries based on morphometrically generated visual guides.

Science.gov (United States)

Barth, Rolf F; Kellough, David A; Allenby, Patricia; Blower, Luke E; Hammond, Scott H; Allenby, Greg M; Buja, L Maximilian

Determination of the degree of stenosis of atherosclerotic coronary arteries is an important part of postmortem examination of the heart, but, unfortunately, estimation of the degree of luminal narrowing can be imprecise and tends to be approximations. Visual guides can be useful to assess this, but earlier attempts to develop such guides did not employ digital technology. Using this approach, we have developed two computer-generated morphometric guides to estimate the degree of luminal narrowing of atherosclerotic coronary arteries. The first is based on symmetric or eccentric circular or crescentic narrowing of the vessel lumen and the second on either slit-like or irregularly shaped narrowing of the vessel lumens. Using the Aperio ScanScope XT at a magnification of 20× we created digital whole-slide images of 20 representative microscopic cross sections of the left anterior descending (LAD) coronary artery, stained with either hematoxylin and eosin (H&E) or Movat's pentachrome stain. These cross sections illustrated a variety of luminal profiles and degrees of stenosis. Three representative types of images were selected and a visual guide was constructed with Adobe Photoshop CS5. Using the "Scale" and "Measurement" tools, we created a series of representations of stenosis with luminal cross sections depicting 20%, 40%, 60%, 70%, 80%, and 90% occlusion of the LAD branch. Four pathologists independently reviewed and scored the degree of atherosclerotic luminal narrowing based on our visual guides. In addition, digital technology was employed to determine the degree of narrowing by measuring the cross-sectional area of the 20 microscopic sections of the vessels, first assuming no narrowing and then comparing this to the percent of narrowing determined by precise measurement. Two of the observers were very experienced general autopsy pathologists, one was a first-year pathology resident on his first rotation on the autopsy service, and the fourth observer was a

Prevalence of Atherosclerotic Coronary Stenosis in Asymptomatic North Indian Population: A Post-mortem Coronary Angiography Study.

Science.gov (United States)

Bansal, Yogender Singh; Mandal, Shatrugan Prasad; Kumar, Senthil; Setia, Puneet

2015-09-01

A preliminary study of coronaries using post-mortem angiography was undertaken to see the prevalence of atherosclerotic coronary stenosis in non-cardiac unnatural deaths. This study was conducted in a tertiary care centre located in Chandigarh. A total of 128 medico-legal cases were studied comprising 88 males and 40 females. Post-mortem examinations of these MLC cases were conducted in the Department of Forensic Medicine, PGIMER, Chandigarh. All hearts were visually screened by post-mortem coronary angiography first and then grossly examined using serial transverse incision technique in positive screening cases to find the degree of narrowing. Of the study group, 34% males and 20% females showed evidence of narrowing on angiography. Of the males showing coronary stenosis, 83% had single vessel disease and 13% had double vessel disease, while only one individual had triple vessel disease. In cases of female, all the cases of coronary stenosis were single vessel disease. Left anterior descending coronary artery (LAD) was the most common vessel involved, followed by right coronary artery (RCA) & Left circumflex artery (LCX) and in cases of double vessel disease, LAD in combination with LCX was responsible for 75% of the cases. Remarkably 23.6% of study population in the age group of less than 40 years showed appreciable narrowing in at least one of the coronaries. In general, the prevalence of CAD is on the rise, particularly in younger population owing to the changes in their lifestyle and food habits. This preliminary study revealed evidence of narrowing of at least one coronary in 34% male and 20% female population and 23.6% subjects were less than 40 years old. Further detailed studies are needed especially in younger age group and to support the need for preventive cardiology in the early years of life.

Impact of motion compensation and partial volume correction for 18F-NaF PET/CT imaging of coronary plaque

Science.gov (United States)

Cal-González, J.; Tsoumpas, C.; Lassen, M. L.; Rasul, S.; Koller, L.; Hacker, M.; Schäfers, K.; Beyer, T.

2018-01-01

Recent studies have suggested that 18F-NaF-PET enables visualization and quantification of plaque micro-calcification in the coronary tree. However, PET imaging of plaque calcification in the coronary arteries is challenging because of the respiratory and cardiac motion as well as partial volume effects. The objective of this work is to implement an image reconstruction framework, which incorporates compensation for respiratory as well as cardiac motion (MoCo) and partial volume correction (PVC), for cardiac 18F-NaF PET imaging in PET/CT. We evaluated the effect of MoCo and PVC on the quantification of vulnerable plaques in the coronary arteries. Realistic simulations (Biograph TPTV, Biograph mCT) and phantom acquisitions (Biograph mCT) were used for these evaluations. Different uptake values in the calcified plaques were evaluated in the simulations, while three ‘plaque-type’ lesions of 36, 31 and 18 mm3 were included in the phantom experiments. After validation, the MoCo and PVC methods were applied in four pilot NaF-PET patient studies. In all cases, the MoCo-based image reconstruction was performed using the STIR software. The PVC was obtained from a local projection (LP) method, previously evaluated in preclinical and clinical PET. The results obtained show a significant increase of the measured lesion-to-background ratios (LBR) in the MoCo  +  PVC images. These ratios were further enhanced when using directly the tissue-activities from the LP method, making this approach more suitable for the quantitative evaluation of coronary plaques. When using the LP method on the MoCo images, LBR increased between 200% and 1119% in the simulated data, between 212% and 614% in the phantom experiments and between 46% and 373% in the plaques with positive uptake observed in the pilot patients. In conclusion, we have built and validated a STIR framework incorporating MoCo and PVC for 18F-NaF PET imaging of coronary plaques. First results indicate an improved

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

Science.gov (United States)

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

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

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

KAUST Repository

Hossain, Shaolie S.; Hossainy, Syed F A; Bazilevs, Yuri; Calo, Victor M.; Hughes, Thomas Jr R

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.

Atherectomy devices: technology update

Science.gov (United States)

Akkus, Nuri I; Abdulbaki, Abdulrahman; Jimenez, Enrique; Tandon, Neeraj

2015-01-01

Atherectomy is a procedure which is performed to remove atherosclerotic plaque from diseased arteries. Atherosclerotic plaques are localized in either coronary or peripheral arterial vasculature and may have different characteristics depending on the texture of the plaque. Atherectomy has been used effectively in treatment of both coronary and peripheral arterial disease. Atherectomy devices are designed differently to either cut, shave, sand, or vaporize these plaques and have different indications. In this article, current atherectomy devices are reviewed. PMID:25565904

Fractal analysis of plaque border, a novel method for the quantification of atherosclerotic plaque contour irregularity, is associated with pro-atherogenic plasma lipid profile in subjects with non-obstructive carotid stenoses.

Science.gov (United States)

Moroni, Francesco; Magnoni, Marco; Vergani, Vittoria; Ammirati, Enrico; Camici, Paolo G

2018-01-01

Plaque border irregularity is a known imaging characteristic of vulnerable plaques, but its evaluation heavily relies on subjective evaluation and operator expertise. Aim of the present work is to propose a novel fractal-analysis based method for the quantification of atherosclerotic plaque border irregularity and assess its relation with cardiovascular risk factors. Forty-two asymptomatic subjects with carotid stenosis underwent ultrasound evaluation and assessment of cardiovascular risk factors. Total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) plasma cholesterol and triglycerides concentrations were measured for each subject. Fractal analysis was performed in all the carotid segments affected by atherosclerosis, i.e. 147 segments. The resulting fractal dimension (FD) is a measure of irregularity of plaque profile on long axis view of the plaque. FD in the severest stenosis (main plaque FD,mFD) was 1.136±0.039. Average FD per patient (global FD,gFD) was 1.145±0.039. FD was independent of other plaque characteristics. mFD significantly correlated with plasma HDL (r = -0.367,p = 0.02) and triglycerides-to-HDL ratio (r = 0.480,p = 0.002). Fractal analysis is a novel, readily available, reproducible and inexpensive technique for the quantitative measurement of plaque irregularity. The correlation between low HDL levels and plaque FD suggests a role for HDL in the acquisition of morphologic features of plaque instability. Further studies are needed to validate the prognostic value of fractal analysis in carotid plaques evaluation.

Intravascular photoacoustic imaging of human coronary atherosclerosis

Science.gov (United States)

Jansen, Krista; van der Steen, Antonius F. W.; Springeling, Geert; van Beusekom, Heleen M. M.; Oosterhuis, J. Wolter; van Soest, Gijs

2011-03-01

We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. We specifically imaged lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction. An integrated intravascular photoacoustics (IVPA) and ultrasound (IVUS) catheter with an outer diameter of 1.25 mm was developed. The catheter comprises an angle-polished optical fiber adjacent to a 30 MHz single-element transducer. The ultrasonic transducer was optically isolated to eliminate artifacts in the PA image. We performed measurements on a cylindrical vessel phantom and isolated point targets to demonstrate its imaging performance. Axial and lateral point spread function widths were 110 μm and 550 μm, respectively, for PA and 89 μm and 420 μm for US. We imaged two fresh human coronary arteries, showing different stages of disease, ex vivo. Specific photoacoustic imaging of lipid content, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230 nm.

Advanced computed tomographic anatomical and morphometric plaque analysis for prediction of fractional flow reserve in intermediate coronary lesions

International Nuclear Information System (INIS)

Opolski, Maksymilian P.; Kepka, Cezary; Achenbach, Stephan; Pregowski, Jerzy; Kruk, Mariusz; Staruch, Adam D.; Kadziela, Jacek; Ruzyllo, Witold; Witkowski, Adam

2014-01-01

Objective: To determine the application of advanced coronary computed tomography angiography (CCTA) plaque analysis for predicting invasive fractional flow reserve (FFR) in intermediate coronary lesions. Methods: Sixty-one patients with 71 single intermediate coronary lesions (≥50–80% stenosis) on CCTA prospectively underwent coronary angiography and FFR. Advanced anatomical and morphometric plaque analysis was performed based on CCTA data set to determine optimal criteria for significant flow impairment. A significant stenosis was defined as FFR ≤ 0.80. Results: FFR averaged 0.85 ± 0.09, and 19 lesions (27%) were functionally significant. FFR correlated with minimum lumen area (MLA) (r = 0.456, p < 0.001), minimum lumen diameter (MLD) (r = 0.326, p = 0.006), reference lumen diameter (RLD) (r = 0.245, p = 0.039), plaque burden (r = −0.313, p = 0.008), lumen area stenosis (r = −0.305, p = 0.01), lesion length (r = −0.692, p < 0.001), and plaque volume (r = −0.668, p < 0.001). There was no relationship between FFR and CCTA morphometric plaque parameters. By multivariate analysis the independent predictors of FFR were lesion length (beta = −0.581, p < 0.001), MLA (beta = 0.360, p = 0.041), and RLD (beta = −0.255, p = 0.036). The optimal cutoffs for lesion length, MLA, MLD, RLD, and lumen area stenosis were >18.5 mm, ≤3.0 mm 2 , ≤2.1 mm, ≤3.2 mm, and >69%, respectively (max. sensitivity: 100% for MLA, max. specificity: 79% for lumen area stenosis). Conclusions: CCTA predictors for FFR support the mathematical relationship between stenosis pressure drop and coronary flow. CCTA could prove to be a useful rule-out test for significant hemodynamic effects of intermediate coronary stenoses

Comparison of multislice computed tomography with intravascular ultrasound for detection and characterization of coronary artery plaques: A systematic review

Energy Technology Data Exchange (ETDEWEB)

Springer, Ivonne [Department of Radiology, Charite, Medical School, Humboldt-Universitaet zu Berlin (Germany); Dewey, Marc [Department of Radiology, Charite, Medical School, Humboldt-Universitaet zu Berlin (Germany)], E-mail: marc.dewey@charite.de

2009-08-15

Purpose: Multislice computed tomography (MSCT) is a novel non-invasive test for detection and analysis of coronary artery plaques. A systematic review was conducted of the literature to compare MSCT with IVUS as the reference standard for assessing coronary artery plaques. Materials and methods: We performed a literature search in the online database MEDLINE, which was accessed at (http://www.pubmed.gov) on 9th April 2008. Results: The search identified 14 studies with 340 patients (mean age 59 {+-} 5 years). The systematic review revealed a sensitivity of MSCT on the lesion level (n = 1779 coronary plaques) on the order of 90% (range from 87 to 92%) in comparison to IVUS. Per-segment analysis (n = 356) yielded a lower sensitivity of 81-86%. In the per-vessel analysis (n = 90), MSCT had a better sensitivity and specificity for the RCA (83-89% and 92-100%) and the LAD (83-87% and 93%) than for the LCX (71-85% and 77-89%), and on the vessel level and the cross-section analysis MSCT was more sensitive for calcified plaques than for non-calcified plaque. It is noteworthy that most studies provide only incomplete data on technical and methodological parameters such as radiation exposure and patient characteristics. Conclusion: MSCT is an accurate and reliable test for detection of coronary artery plaques in comparison to IVUS with limitations in regards to the LCX and non-calcified plaques. Studies published thus far are limited by the sample sizes and methodological quality issues.

Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid lowering

Science.gov (United States)

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Iida, Ryuji; Wang, Qilong; Zou, Ming-Hui; Barlic-Dicen, Jana

2012-01-01

The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression. We tested our hypothesis in the atherosclerosis-prone mouse model in which hypercholesterolemia, one of the main factors affecting EPC homeostasis, is reversible (Reversa mice). In these mice normalization of plasma lipids decreased atherosclerotic burden; however, plaque regression was incomplete. To explore whether endothelial progenitors contribute to atherosclerosis regression, bone marrow EPCs from a transgenic strain expressing green fluorescent protein under the control of endothelial cell-specific Tie2 promoter (Tie2-GFP+) were isolated. These cells were then adoptively transferred into atheroregressing Reversa recipients where they augmented plaque regression induced by reversal of hypercholesterolemia. Advanced plaque regression correlated with engraftment of Tie2-GFP+ EPCs into endothelium and resulted in an increase in atheroprotective nitric oxide and improved vascular relaxation. Similarly augmented plaque regression was also detected in regressing Reversa mice treated with the stem cell mobilizer AMD3100 which also mobilizes EPCs to peripheral blood. We conclude that correction of hypercholesterolemia in Reversa mice leads to partial plaque regression that can be augmented by AMD3100 treatment or by adoptive transfer of EPCs. This suggests that direct cell therapy or indirect progenitor cell mobilization therapy may be used in combination with statins to treat atherosclerosis. PMID:23081735

Therapeutic modulation of the natural history of coronary atherosclerosis: lessons learned from serial imaging studies.

Science.gov (United States)

Andrews, Jordan; Puri, Rishi; Kataoka, Yu; Nicholls, Stephen J; Psaltis, Peter J

2016-08-01

Despite advances in risk prediction, preventive and therapeutic strategies, atherosclerotic cardiovascular disease remains a major public health challenge worldwide, carrying considerable morbidity, mortality and health economic burden. There continues to be a need to better understand the natural history of this disease to guide the development of more effective treatment, integral to which is the rapidly evolving field of coronary artery imaging. Various imaging modalities have been refined to enable detailed visualization of the pathological substrate of atherosclerosis, providing accurate and reproducible measures of coronary plaque burden and composition, including the presence of high-risk characteristics. The serial application of such techniques, including coronary computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have uncovered important insights into the progression of coronary plaque over time in patients with stable and unstable coronary artery disease (CAD), and its responsiveness to therapeutic interventions. Here we review the use of different imaging modalities for the surveillance of coronary atherosclerosis and the lessons they have provided about the modulation of CAD by both traditional and experimental therapies.

Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis

Directory of Open Access Journals (Sweden)

Xiaowen Tan

2017-01-01

Full Text Available Background. Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. Methods. Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO, including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs were analyzed. Results. 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton. Conclusion. The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.

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....

Clinical Relevance of 18F-Sodium Fluoride Positron-Emission Tomography in Noninvasive Identification of High-Risk Plaque in Patients With Coronary Artery Disease.

Science.gov (United States)

Lee, Joo Myung; Bang, Ji-In; Koo, Bon-Kwon; Hwang, Doyeon; Park, Jonghanne; Zhang, Jinlong; Yaliang, Tong; Suh, Minseok; Paeng, Jin Chul; Shiono, Yasutsugu; Kubo, Takashi; Akasaka, Takashi

2017-11-01

18 F-sodium fluoride ( 18 F-NaF) positron-emission tomography has been introduced as a potential noninvasive imaging tool to identify plaques with high-risk characteristics in patients with coronary artery disease. We sought to evaluate the clinical relevance of 18 F-NaF uptake using optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography in patients with coronary artery disease. The target population consisted of 51 prospectively enrolled patients (93 stenoses) who underwent 18 F-NaF positron-emission tomography before invasive coronary angiography. 18 F-NaF uptake was compared with IVUS- and OCT-derived plaque characteristics. In the coronary computed tomography angiography subgroup (46 lesions), qualitative lesion characteristics were compared between 18 F-NaF-positive and 18 F-NaF-negative plaques using adverse plaque characteristics. The plaques with 18 F-NaF uptake showed significantly higher plaque burden, more frequent posterior attenuation and positive remodeling in IVUS, and significantly higher maximum lipid arc and more frequent microvessels in OCT (all P characteristics. The 18 F-NaF tissue-to-background ratio in plaques with high-risk characteristics was significantly higher than in those without (1.09 [95% confidence interval, 0.85-1.34] versus 0.62 [95% confidence interval, 0.42-0.82], P characteristics between 18 F-NaF-positive and 18 F-NaF-negative plaques in the coronary computed tomography angiography subgroup (85.2% versus 78.9%; P =0.583). This study's results suggest that 18 F-NaF positron-emission tomography can be a useful noninvasive diagnostic tool to identify and localize plaque with high-risk characteristics. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02388412. © 2017 American Heart Association, Inc.

Volumetric analysis of coronary plaque characterization in patients with metabolic syndrome using 64-slice multi-detector computed tomography

International Nuclear Information System (INIS)

Arai, Kosuke; Ishii, Hideki; Amano, Tetasuya

2010-01-01

Metabolic syndrome (MetS) is associated with adverse cardiovascular events and mortality, where acute coronary syndrome significantly impacts on mortality and morbidity. In contrast, evidences have accumulated that the lipid-rich plaque might play a critical role in acute coronary syndrome. The study population consisted of 94 patients with suspected angina pectoris who underwent multi-detector computed tomography (MDCT). Of those, we identified 41 with MetS. In MDCT analysis, low-density plaque volume (LDPV) (42±28 vs 24±18 mm 3 , P=0.0003), moderate-density plaque volume (105±41 vs 82±33 mm(3), P=0.003), total plaque volume (164±70 vs 118±59 mm 3 ), P=0.0008) and %LDPV (24.2±10.0 vs 18.3±7.1%, P=0.01) were significantly increased in the MetS group compared to the non-MetS group. Multivariate linear regression analysis after adjusting for confounding variables revealed that MetS was significantly correlated with an increase in %LDPV (β=0.48, P=0.0001). Multivariate logistic regression analysis for lipid-rich plaque after adjusting for confounding variables indicated that MetS was significantly associated with lipid-rich plaque (odds ratio: 5.99, 95% confidence intervals: 1.94-18.6, P=0.002). Patients with MetS were strongly related to having a lipid-rich composition in their coronary plaque, as detected by MDCT. (author)

Electrical impedance of layered atherosclerotic plaques on human aortas

NARCIS (Netherlands)

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

1992-01-01

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

Iterative model reconstruction reduces calcified plaque volume in coronary CT angiography

Energy Technology Data Exchange (ETDEWEB)

Károlyi, Mihály, E-mail: mihaly.karolyi@cirg.hu [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); Szilveszter, Bálint, E-mail: szilveszter.balint@gmail.com [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); Kolossváry, Márton, E-mail: martonandko@gmail.com [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); Takx, Richard A.P, E-mail: richard.takx@gmail.com [Department of Radiology, University Medical Center Utrecht, 100 Heidelberglaan, 3584, CX Utrecht (Netherlands); Celeng, Csilla, E-mail: celengcsilla@gmail.com [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); Bartykowszki, Andrea, E-mail: bartyandi@gmail.com [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); Jermendy, Ádám L., E-mail: adam.jermendy@gmail.com [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); Panajotu, Alexisz, E-mail: panajotualexisz@gmail.com [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); Karády, Júlia, E-mail: karadyjulia@gmail.com [MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st, 1122, Budapest (Hungary); and others

2017-02-15

Objective: To assess the impact of iterative model reconstruction (IMR) on calcified plaque quantification as compared to filtered back projection reconstruction (FBP) and hybrid iterative reconstruction (HIR) in coronary computed tomography angiography (CTA). Methods: Raw image data of 52 patients who underwent 256-slice CTA were reconstructed with IMR, HIR and FBP. We evaluated qualitative, quantitative image quality parameters and quantified calcified and partially calcified plaque volumes using automated software. Results: Overall qualitative image quality significantly improved with HIR as compared to FBP, and further improved with IMR (p < 0.01 all). Contrast-to-noise ratios were improved with IMR, compared to HIR and FBP (51.0 [43.5–59.9], 20.3 [16.2–25.9] and 14.0 [11.2–17.7], respectively, all p < 0.01) Overall plaque volumes were lowest with IMR and highest with FBP (121.7 [79.3–168.4], 138.7 [90.6–191.7], 147.0 [100.7–183.6]). Similarly, calcified volumes (>130 HU) were decreased with IMR as compared to HIR and FBP (105.9 [62.1–144.6], 110.2 [63.8–166.6], 115.9 [81.7–164.2], respectively, p < 0.05 all). High-attenuation non-calcified volumes (90–129 HU) yielded similar values with FBP and HIR (p = 0.81), however it was lower with IMR (p < 0.05 both). Intermediate- (30–89 HU) and low-attenuation (<30 HU) non-calcified volumes showed no significant difference (p = 0.22 and p = 0.67, respectively). Conclusions: IMR improves image quality of coronary CTA and decreases calcified plaque volumes.

In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR-/-ApoB100/100 mice.

Science.gov (United States)

Blanco, Fabiana; Heinonen, Suvi E; Gurzeler, Erika; Berglund, Lisa M; Dutius Andersson, Anna-Maria; Kotova, Olga; Jönsson-Rylander, Ann-Cathrine; Ylä-Herttuala, Seppo; Gomez, Maria F

2018-03-01

Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated the effects of nuclear factor of activated T-cells inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease. IGF-II/LDLR -/- ApoB 100/100 mice were generated by crossbreeding low-density lipoprotein receptor-deficient mice that synthesize only apolipoprotein B100 (LDLR -/- ApoB 100/100 ) with transgenic mice overexpressing insulin-like growth factor-II in pancreatic β cells. Mice have mild hyperglycaemia and hyperinsulinaemia and develop complex atherosclerotic lesions. In vivo treatment with the nuclear factor of activated T-cells blocker A-285222 for 4 weeks reduced atherosclerotic plaque area and degree of stenosis in the brachiocephalic artery of IGF-II/LDLR -/- ApoB 100/100 mice, as assessed non-invasively using ultrasound biomicroscopy prior and after treatment, and histologically after termination. Treatment had no impact on plaque composition (i.e. muscle, collagen, macrophages). The reduced plaque area could not be explained by effects of A-285222 on plasma glucose, insulin or lipids. Inhibition of nuclear factor of activated T-cells was associated with increased expression of atheroprotective NOX4 and of the anti-oxidant enzyme catalase in aortic vascular smooth muscle cells. Targeting the nuclear factor of activated T-cells signalling pathway may be an attractive approach for the treatment of diabetic macrovascular complications.

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

Science.gov (United States)

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

2016-05-01

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

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

Correlation between genetic polymorphism of matrix metalloproteinase-9 in patients with coronary artery disease and cardiac remodeling.

Science.gov (United States)

Yu, Qibin; Li, Hanmei; Li, Linlin; Wang, Shaoye; Wu, Yongbo

2015-01-01

To explore the correlation between genetic polymorphism of matrix metalloproteinase-9 (MMP-9) in patients with coronary artery disease (CAD) and cardiac remodeling. A total of 272 subjects who received coronary angiography in our hospital from July 2008 to September 2013 were selected, including 172 CAD patients (CAD group) and another 100 ones (control group). Both groups were subjected to MMP-9 and ultrasonic detections to determine vascular remodeling and atherosclerotic plaques. C1562G polymorphism of MMP-9 gene was detected, and correlation with vascular remodeling and atherosclerotic plaque was analyzed. Serum MMP-9 level of CAD group (330.87±50.39 ng/ml) was significantly higher than that of control group (134.87±34.02 ng/ml) (P<0.05). Compared with control group, CAD group had significantly higher intima-media thickness, and significantly lower systolic peak velocity, mean systolic velocity and end-diastolic velocity (P<0.05). Total area of stenotic blood vessels was 67.34±22.98 mm(2), while that of control blood vessels was 64.00±20.83 mm(2). G/G, G/C and C/C genotype frequencies of MMP-9 differed significantly in the two groups (P<0.05). G and C allele frequencies of CAD group (70.9% and 29.1%) were significantly different from those of control group (50.0% and 50.0%) (P<0.05). G/G, G/C and C/C genotypes were manifested as lipid-rich, fibrous and calcified or ulcerated plaques respectively. Total area of stenotic blood vessels of G/G genotype significantly exceeded those of G/C and C/C genotypes (P<0.05), whereas the latter two had no significant differences. CAD promoted 1562C-G transformation of MMP-9 gene into genetic polymorphism, thus facilitating arterial remodeling and increasing unstable atherosclerotic plaques.

First experiences with model based iterative reconstructions influence on quantitative plaque volume and intensity measurements in coronary computed tomography angiography

International Nuclear Information System (INIS)

Precht, H.; Kitslaar, P.H.; Broersen, A.; Gerke, O.; Dijkstra, J.; Thygesen, J.; Egstrup, K.; Lambrechtsen, J.

2017-01-01

Purpose: Investigate the influence of adaptive statistical iterative reconstruction (ASIR) and the model-based IR (Veo) reconstruction algorithm in coronary computed tomography angiography (CCTA) images on quantitative measurements in coronary arteries for plaque volumes and intensities. Methods: Three patients had three independent dose reduced CCTA performed and reconstructed with 30% ASIR (CTDI vol at 6.7 mGy), 60% ASIR (CTDI vol 4.3 mGy) and Veo (CTDI vol at 1.9 mGy). Coronary plaque analysis was performed for each measured CCTA volumes, plaque burden and intensities. Results: Plaque volume and plaque burden show a decreasing tendency from ASIR to Veo as median volume for ASIR is 314 mm 3 and 337 mm 3 –252 mm 3 for Veo and plaque burden is 42% and 44% for ASIR to 39% for Veo. The lumen and vessel volume decrease slightly from 30% ASIR to 60% ASIR with 498 mm 3 –391 mm 3 for lumen volume and vessel volume from 939 mm 3 to 830 mm 3 . The intensities did not change overall between the different reconstructions for either lumen or plaque. Conclusion: We found a tendency of decreasing plaque volumes and plaque burden but no change in intensities with the use of low dose Veo CCTA (1.9 mGy) compared to dose reduced ASIR CCTA (6.7 mGy & 4.3 mGy), although more studies are warranted. - Highlights: • Veo decrease plaque volumes and plaque burden using low-dose CCTA. • Moving from ASIR 30%, ASIR 60% to Veo did not appear to influence the plaque intensities. • Studies including larger sample size are needed to investigate the effect on plaque.

Association of traditional cardiovascular risk factors with coronary plaque sub-types assessed by 64-slice computed tomography angiography in a large cohort of asymptomatic subjects.

Science.gov (United States)

Rivera, Juan J; Nasir, Khurram; Cox, Pedro R; Choi, Eue-Keun; Yoon, Yeonyee; Cho, Iksung; Chun, Eun-Ju; Choi, Sang-Il; Blumenthal, Roger S; Chang, Hyuk-Jae

2009-10-01

Although prior studies have shown that traditional cardiovascular (CV) risk factors are associated with the burden of coronary atherosclerosis, less is known about the relationship of risk factors with coronary plaque sub-types. Coronary computed tomography angiography (CCTA) allows an assessment of both, total disease burden and plaque characteristics. In this study, we investigate the relationship between traditional CV risk factors and the presence and extent of coronary plaque sub-types in a large group of asymptomatic individuals. The study population consisted of 1015 asymptomatic Korean subjects (53+/-10 years; 64% were males) free of known CV disease who underwent 64-slice CCTA as part of a health screening evaluation. We analyzed plaque characteristics on a per-segment basis according to the modified American Heart Association classification. Plaques in which calcified tissue occupied more than 50% of the plaque area were classified as calcified (CAP), NCAP). A total of 215 (21%) subjects had coronary plaque while 800 (79%) had no identifiable disease. Multivariate regression analysis demonstrated that increased age (per decade) and gender are the strongest predictors for the presence of any coronary plaque or the presence of at least one segment of CAP and MCAP (any plaque-age: OR 2.89; 95% CI 2.34, 3.56; male gender: OR 5.21; 95% CI 3.20, 8.49; CAP-age: OR 2.75; 95% CI 2.12, 3.58; male gender: 4.78; 95% CI 2.48, 9.23; MCAP-age: OR 2.62; 95% CI 2.02, 3.39; male gender: OR 4.15; 95% CI 2.17, 7.94). The strongest predictors for the presence of any NCAP were gender (OR 3.56; 95% CI 1.96-6.55) and diabetes mellitus (OR 2.87; 95% CI 1.63-5.08). When looking at the multivariate association between the presence of >/=2 coronary segments with a plaque sub-type and CV risk factors, male gender was the strongest predictor for CAP (OR 7.31; 95% CI 2.12, 25.20) and MCAP (OR 5.54; 95% CI 1.84, 16.68). Alternatively, smoking was the strongest predictor for the presence

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

International Nuclear Information System (INIS)

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

2011-01-01

Objective: To explore the imaging of the thrombosis after pharmacological triggering of plaque rupture in atherosclerotic rabbit model by using 3.0 T high-resolution magnetic resonance imaging. Methods: Twenty male New Zealand white rabbits were divided into an experimental group (n=16) and a control group (n=4). The aortic wall injuries were induced by an intravascular balloon in experimental group rabbits after high cholesterol diet. The pharmacological triggering with Russell's viper venom and histamine was performed after 3 months of establishment of model. All of the animals underwent pre-trigger and post-trigger MR examinations including 3D time of fight (3D TOF), T 1 WI, T 2 WI and post contrast T 1 WI. Euthanasia was performed in all rabbits and gross anatomy and histological specimen of aorta were obtained. Comparing the location and length of the thrombus between MRI images and histopathology was used Pearson test. Comparing the calculated indexes of abdominal aorta between rabbits with and without thrombosis was used AVONA test and LSD-t test. Results: After triggering, 8 in 14 survived rabbits developed thrombosis in experimental group, meanwhile, no thrombus was found in control group. The accuracy of multi-sequences MRI for detecting of thrombus was 87.1% (27/31). MRI data correlated with the histopathology regarding thrombus length (r=0.85, P 2 vs. (8.93±5.36) mm 2 , P<0.01]. Conclusion: MRI is useful tool to determine the thrombosis and plaque rupture in atherosclerotic rabbit model. (authors)

Association of aortic valve calcification to the presence, extent, and composition of coronary artery plaque burden: from the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) trial.

Science.gov (United States)

Mahabadi, Amir A; Bamberg, Fabian; Toepker, Michael; Schlett, Christopher L; Rogers, Ian S; Nagurney, John T; Brady, Thomas J; Hoffmann, Udo; Truong, Quynh A

2009-10-01

Aortic valve calcification (AVC) is associated with cardiovascular risk factors and coronary artery calcification. We sought to determine whether AVC is associated with the presence and extent of overall plaque burden, as well as to plaque composition (calcified, mixed, and noncalcified). We examined 357 subjects (mean age 53 +/- 12 years, 61% male) who underwent contrast-enhanced electrocardiogram-gated 64-slice multidetector computed tomography from the ROMICAT trial for the assessment of presence and extent of coronary plaque burden according to the 17-coronary segment model and presence of AVC. Patients with AVC (n = 37, 10%) were more likely than those without AVC (n = 320, 90%) to have coexisting presence of any coronary plaque (89% vs 46%, P AVC had >3-fold increase odds of having any plaque (adjusted odds ratio [OR] 3.6, P = .047) and an increase of 2.5 segments of plaque (P AVC. When stratified by plaque composition, AVC was associated most with calcified plaque (OR 5.2, P = .004), then mixed plaque (OR 3.2, P = .02), but not with noncalcified plaque (P = .96). Aortic valve calcification is associated with the presence and greater extent of coronary artery plaque burden and may be part of the later stages of the atherosclerosis process, as its relation is strongest with calcified plaque, less with mixed plaque, and nonsignificant with noncalcified plaque. If AVC is present, consideration for aggressive medical therapy may be warranted.

MR plaque imaging of the carotid artery

International Nuclear Information System (INIS)

Watanabe, Yuji; Nagayama, Masako

2010-01-01

Atherosclerotic carotid plaque represents a major cause of cerebral ischemia. The detection of vulnerable plaque is important for preventing future cardiovascular events. The key factors in advanced plaque that are most likely to lead to patient complications are the condition of the fibrous cap, the size of the necrotic core and hemorrhage, and the extent of inflammatory activity within the plaque. Magnetic resonance (MR) imaging has excellent soft tissue contrast and can allow for a more accurate and objective estimation of carotid wall morphology and plaque composition. Recent advances in MR imaging techniques have permitted serial monitoring of atherosclerotic disease evolution and the identification of intraplaque risk factors for accelerated progression. The purpose of this review article is to review the current state of techniques of carotid wall MR imaging and the characterization of plaque components and surface morphology with MR imaging, and to describe the clinical practice of carotid wall MR imaging for the determination of treatment plan. (orig.)

Intensive lipid-lowering therapy with rosuvastatin stabilizes lipid-rich coronary plaques. Evaluation using dual-source computed tomography

International Nuclear Information System (INIS)

Soeda, Tsunenari; Uemura, Shiro; Okayama, Satoshi

2011-01-01

Clinical studies using invasive modalities have reported that statin therapy stabilizes coronary plaque vulnerability. The serial changes of lipid-rich coronary plaques (LRCPs) during rosuvastatin treatment were evaluated non-invasively in patients with acute coronary syndrome (ACS) using dual-source computed tomography (DSCT). A total of 11 consecutive ACS patients, and 13 LRCPs were serially evaluated on DSCT before and 24 weeks after rosuvastatin treatment. Compared with the baseline, there was no change in post-treatment minimal lumen diameter, lumen volume, or longitudinal length of LRCPs. By contrast, the ratio of lipid core volume to plaque volume significantly decreased from 48.0±9.9% to 43.7±10.6% (P=0.04), and plaque volume decreased from 144.5±85.5 mm 3 to 119.8±78.0 mm 3 (P=0.07). The remodeling index of target LRCPs significantly decreased from 1.16±0.10 to 1.06±0.12 (P=0.02). Percent reduction of plaque volume was significantly greater in patients with a lower ratio of low-density lipoprotein to high-density lipoprotein (L/H ratio ≤1.5) at follow-up than patients with higher L/H ratio (>1.5; median -31.7% vs. -6.8%, P=0.03). Rosuvastatin therapy reduced the volume of lipid cores and LRCPs and increased the CT attenuation value of LRCPs. DSCT is an effective modality for the non-invasive evaluation of LRCPs in patients with ACS. (author)

Framework for detection and localization of coronary non-calcified plaques in cardiac CTA using mean radial profiles.

Science.gov (United States)

Jawaid, Muhammad Moazzam; Riaz, Atif; Rajani, Ronak; Reyes-Aldasoro, Constantino Carlos; Slabaugh, Greg

2017-10-01

The high mortality rate associated with coronary heart disease (CHD) has driven intensive research in cardiac imaging and image analysis. The advent of computed tomography angiography (CTA) has turned non-invasive diagnosis of cardiovascular anomalies into reality as calcified coronary plaques can be easily identified due to their high intensity values. However, the detection of non-calcified plaques in CTA is still a challenging problem because of lower intensity values, which are often similar to the nearby blood and muscle tissues. In this work, we propose the use of mean radial profiles for the detection of non-calcified plaques in CTA imagery. Accordingly, we computed radial profiles by averaging the image intensity in concentric rings around the vessel centreline in a first stage. In the subsequent stage, an SVM classifier is applied to identify the abnormal coronary segments. For occluded segments, we further propose a derivative-based method to localize the position and length of the plaque inside the segment. A total of 32 CTA volumes were analysed and a detection accuracy of 88.4% with respect to the manual expert was achieved. The plaque localization accuracy was computed using the Dice similarity coefficient and a mean of 83.2% was achieved. The consistent performance for multi-vendor, multi-institution data demonstrates the reproducibility of our method across different CTA datasets with a good agreement with manual expert annotations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coronary artery plaques: Cardiac CT with model-based and adaptive-statistical iterative reconstruction technique

International Nuclear Information System (INIS)

Scheffel, Hans; Stolzmann, Paul; Schlett, Christopher L.; Engel, Leif-Christopher; Major, Gyöngi Petra; Károlyi, Mihály; Do, Synho; Maurovich-Horvat, Pál; Hoffmann, Udo

2012-01-01

Objectives: To compare image quality of coronary artery plaque visualization at CT angiography with images reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model based iterative reconstruction (MBIR) techniques. Methods: The coronary arteries of three ex vivo human hearts were imaged by CT and reconstructed with FBP, ASIR and MBIR. Coronary cross-sectional images were co-registered between the different reconstruction techniques and assessed for qualitative and quantitative image quality parameters. Readers were blinded to the reconstruction algorithm. Results: A total of 375 triplets of coronary cross-sectional images were co-registered. Using MBIR, 26% of the images were rated as having excellent overall image quality, which was significantly better as compared to ASIR and FBP (4% and 13%, respectively, all p < 0.001). Qualitative assessment of image noise demonstrated a noise reduction by using ASIR as compared to FBP (p < 0.01) and further noise reduction by using MBIR (p < 0.001). The contrast-to-noise-ratio (CNR) using MBIR was better as compared to ASIR and FBP (44 ± 19, 29 ± 15, 26 ± 9, respectively; all p < 0.001). Conclusions: Using MBIR improved image quality, reduced image noise and increased CNR as compared to the other available reconstruction techniques. This may further improve the visualization of coronary artery plaque and allow radiation reduction.

Prognostic value of atherosclerotic burden and coronary vascular function in patients with suspected coronary artery disease

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Assante, Roberta; Zampella, Emilia; Nappi, Carmela; Mainolfi, Ciro Gabriele; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Acampa, Wanda [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Arumugam, Parthiban; Tonge, Christine M. [Central Manchester University Teaching Hospitals, Nuclear Medicine Center, Manchester (United Kingdom); Gaudieri, Valeria; Panico, Mariarosaria; Magliulo, Mario [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy)

2017-12-15

To evaluate the prognostic value of coronary atherosclerotic burden, assessed by coronary artery calcium (CAC) score, and coronary vascular function, assessed by coronary flow reserve (CFR) in patients with suspected coronary artery disease (CAD). We studied 436 patients undergoing hybrid {sup 82}Rb positron emission tomography/computed tomography imaging. CAC score was measured according to the Agatston method, and patients were categorized into three groups (0, <400, and ≥400). CFR was calculated as the ratio of hyperemic to baseline myocardial blood flow, and it was considered reduced when <2. Follow-up was 94% complete during a mean period of 47±15 months. During follow-up, 17 events occurred (4% cumulative event rate). Event-free survival decreased with worsening of CAC score category (p < 0.001) and in patients with reduced CFR (p < 0.005). At multivariable analysis, CAC score ≥400 (p < 0.01) and CFR (p < 0.005) were independent predictors of events. Including CFR in the prognostic model, continuous net reclassification improvement was 0.51 (0.14 in patients with events and 0.37 in those without). At classification and regression tree analysis, the initial split was on CAC score. For patients with a CAC score < 400, no further split was performed, while patients with a CAC score ≥400 were further stratified by CFR values. Decision curve analyses indicate that the model including CFR resulted in a higher net benefit across a wide range of decision threshold probabilities. In patients with suspected CAD, CFR provides significant incremental risk stratification over established cardiac risk factors and CAC score for prediction of adverse cardiac events. (orig.)

Non-calcified coronary plaque volume inversely related to CD4 count in HIV infection

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Duarte, Horacio; Matta, Jatin R.; Muldoon, Nancy; Masur, Henry; Hadigan, Colleen; Gharib, Ahmed M.

2013-01-01

Background Non-calcified coronary artery plaque (NCAP) may be an important predictor of cardiovascular events, however, few studies have directly measured NCAP in HIV-infected individuals. Methods We completed a prospective cross-sectional evaluation of NCAP and coronary calcium scores using CT angiography in HIV-infected subjects (n=26) without known coronary artery disease (CAD), but who had one or more CAD risk factor and compared them to controls matched on age, race, sex, body mass index and Framingham risk score (n=26). Results There was no difference in coronary calcium scores (114 ± 218 vs. 124 ± 298 p=0.89) or NCAP volume (65 ± 86 mm3 vs. 63 ± 82 mm3, p=0.38) between HIV-infected subjects and controls, respectively. Among HIV-infected subjects, lower CD4 count was associated with increased NCAP volume (r=-0.52, p=0.006). CD4 count remained a significant predictor of NCAP in a multivariate analysis that adjusted for age and duration of antiretroviral therapy. Conclusion Plaque burden is similar between HIV-infected and uninfected individuals when matched on traditional CAD risk factors, however immune function may mediate the development of atherosclerosis in HIV infection. PMID:22293714

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

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Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

2017-02-01

The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

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

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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

Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

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Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

2011-01-01

Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

Characteristic detected on computed tomography angiography predict coronary artery plaque progression in non-culprit lesions

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Tan, Ya Hang; Zhou, Jia Zhou; Zhou, Ying; Yang, Xiaobo; Yang, Jun Jie; Chen, Yun Dai [Dept. of Cardiology, Chinese PLA General Hospital, Beijing (China)

2017-06-15

This study sought to determine whether variables detected on coronary computed tomography angiography (CCTA) would predict plaque progression in non-culprit lesions (NCL). In this single-center trial, we analyzed 103 consecutive patients who were undergoing CCTA and percutaneous coronary intervention (PCI) for culprit lesions. Follow-up CCTA was scheduled 12 months after the PCI, and all patients were followed for 3 years after their second CCTA examination. High-risk plaque features and epicardial adipose tissue (EAT) volume were assessed by CCTA. Each NCL stenosis grade was compared visually between two CCTA scans to detect plaque progression, and patients were stratified into two groups based on this. Logistic regression analysis was used to evaluate the factors that were independently associated with plaque progression in NCLs. Time-to-event curves were compared using the log-rank statistic. Overall, 34 of 103 patients exhibited NCL plaque progression (33%). Logistic regression analyses showed that the NCL progression was associated with a history of ST-elevated myocardial infarction (odds ratio [OR] = 5.855, 95% confidence interval [CI] = 1.391–24.635, p = 0.016), follow-up low-density lipoprotein cholesterol level (OR = 6.832, 95% CI = 2.103–22.200, p = 0.001), baseline low-attenuation plaque (OR = 7.311, 95% CI = 1.242–43.028, p = 0.028) and EAT (OR = 1.015, 95% CI = 1.000–1.029, p = 0.044). Following the second CCTA examination, major adverse cardiac events (MACEs) were observed in 12 patients, and NCL plaque progression was significantly associated with future MACEs (log rank p = 0.006). Noninvasive assessment of NCLs by CCTA has potential prognostic value.

Influence of increasing convolution kernel filtering on plaque imaging with multislice CT using an ex-vivo model of Coronary Angiography

International Nuclear Information System (INIS)

Cademartiri, Filippo; Mollet, Nico R.; Runza, Giuseppe

2005-01-01

Purpose. To assess the variability in attenuation of coronary plaques with multislice CT angiography (MSCT-CA) in an ex-vivo model with varying convolution kernels. Materials and methods. MSCT-CA (Sensation 16, Siemens) was performed in three ex-vivo left coronary arteries after instillation of contrast material solution (Iomeprol 400 mgI/ml, dilution: 1180). The specimens were placed in oil to simulate epicardial fat. Scan parameters: slices 16/0.75 mm, rotation time 375 ms, feed/rotation 3.0 mm, mAs 500, slice thickness 1 mm, and FOV 50 mm. Datasets were reconstructed using 4 different kernels (B30f-smooth, B36f-medium smooth, B46f medium, and B60f-sharp). Each scan was scored for the presence of plaques. Once a plaque was detected, the operator performed attenuation measurements (HU) in coronary lumen, oil, calcified and soft plaque tissue using the same settings in all datasets. The results were compared with T-test and correlated with Pearson's test. Results. Overall, 464 measurements were performed. Significant differences (p [it

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

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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.

Incremental prognostic value of coronary computed tomographic angiography high-risk plaque characteristics in newly symptomatic patients.

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Fujimoto, Shinichiro; Kondo, Takeshi; Takamura, Kazuhisa; Baber, Usman; Shinozaki, Tomohiro; Nishizaki, Yuji; Kawaguchi, Yuko; Matsumori, Rie; Hiki, Makoto; Miyauchi, Katsumi; Daida, Hiroyuki; Hecht, Harvey; Stone, Gregg W; Narula, Jagat

2016-06-01

The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p=0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p=0.812). However, improved model-fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p=0.007 from likelihood ratio test) and the lowest value of Akaike's information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Porphyromonas gingivalis-dendritic cell interactions: consequences for coronary artery disease.

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Zeituni, Amir E; Carrion, Julio; Cutler, Christopher W

2010-12-21

An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture.

Porphyromonas gingivalis–dendritic cell interactions: consequences for coronary artery disease

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Amir E. Zeituni

2010-12-01

Full Text Available An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture.

Novel Approaches for the Use of Cardiac/Coronary Computed Tomography Angiography

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Hadi Mirhedayati Roudsari, MD

2016-12-01

Full Text Available Recent developments in the novel imaging technology of cardiac computed tomography (CT not only permit detailed assessment of cardiac anatomy but also provide insight into cardiovascular physiology. Foremost, coronary CT angiography (CCTA enables direct noninvasive examination of both coronary artery stenoses and atherosclerotic plaque characteristics. Calculation of computational fluid dynamics by cardiac CT allows the noninvasive estimation of fractional flow reserve, which increases the diagnostic accuracy for detection of hemodynamically significant coronary artery disease. In addition, a combination of myocardial CT perfusion and CCTA can provide simultaneous anatomical and functional assessment of coronary artery disease. Finally, detailed anatomical evaluation of atrial, ventricular, and valvular anatomy provides diagnostic information and guidance for procedural planning, such as for transcatheter aortic valve replacement. The clinical applications of cardiac CT will be extended with the development of these novel modalities.

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

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2012-01-01

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

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

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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.

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

DEFF Research Database (Denmark)

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

2014-01-01

atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n.......4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P high SCORE or intermediate or high FRS (all P ..., with moderate SCORE or with high-intermediate or high FRS (all P high FRS (P 

Influence of convolution filtering on coronary plaque attenuation values: observations in an ex vivo model of multislice computed tomography coronary angiography

International Nuclear Information System (INIS)

Cademartiri, Filippo; Palumbo, Alessandro; La Grutta, Ludovico; Runza, Giuseppe; Maffei, Erica; Mollet, Nico R.; Hamers, Ronald; Bruining, Nico; Bartolotta, Tommaso V.; Midiri, Massimo; Somers, Pamela; Knaapen, Michiel; Verheye, Stefan

2007-01-01

Attenuation variability (measured in Hounsfield Units, HU) of human coronary plaques using multislice computed tomography (MSCT) was evaluated in an ex vivo model with increasing convolution kernels. MSCT was performed in seven ex vivo left coronary arteries sunk into oil followingthe instillation of saline (1/∞) and a 1/50 solution of contrast material (400 mgI/ml iomeprol). Scan parameters were: slices/collimation, 16/0.75 mm; rotation time, 375 ms. Four convolution kernels were used: b30f-smooth, b36f-medium smooth, b46f-medium and b60f-sharp. An experienced radiologist scored for the presence of plaques and measured the attenuation in lumen, calcified and noncalcified plaques and the surrounding oil. The results were compared by the ANOVA test and correlated with Pearson's test. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The mean attenuation values were significantly different between the four filters (p < 0.0001) in each structure with both solutions. After clustering for the filter, all of the noncalcified plaque values (20.8 ± 39.1, 14.2 ± 35.8, 14.0 ± 32.0, 3.2 ± 32.4 HU with saline; 74.7 ± 66.6, 68.2 ± 63.3, 66.3 ± 66.5, 48.5 ± 60.0 HU in contrast solution) were significantly different, with the exception of the pair b36f-b46f, for which a moderate-high correlation was generally found. Improved SNRs and CNRs were achieved by b30f and b46f. The use of different convolution filters significantly modified the attenuation values, while sharper filtering increased the calcified plaque attenuation and reduced the noncalcified plaque attenuation. (orig.)

Atheroprotective Properties of Serum IGF-1 in the Carotid and Coronary Territories and Beneficial Role on the Physical Fitness of the Oldest Old.

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Córdova, Claudio; Boullosa, Daniel A; Custódio, Misael R M; Quaglia, Luiz A; Santos, Simone N; Freitas, Wladimir M; Sposito, Andrei C; Nóbrega, Otávio T

2016-10-01

Our aim was to investigate whether physiological levels of soluble insulin-like growth factor-1 (IGF-1) associate with coronary and carotid atherosclerotic burden and physical fitness in the oldest old by means of a cross-sectional study including 100 community-dwelling individuals with no previous cardiovascular events. Linear correlation was found between IGF-1 and intima-media thickness, number of carotid plaques, and walking speed. Individuals in the upper IGF-1 tertile had smaller right and left intima-media thickness compared with the intermediate and lower tertiles, along with reduced atherosclerotic plaques. Also, walking speed was greater in the upper IGF-1 tertile. On the other hand, a nonlinear correlation was observed between IGF-1 and coronary calcification scores, with the intermediate IGF-1 tertile associated to the lowest scores of calcification and participants with lower circulating levels of IGF-1 showing higher frequency of high-risk morphology plaques. All in all, our report supports a territory-dependent, atherorefractory phenotype in the oldest old carrying middle and/or higher serum levels of IGF-1. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study.

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Soe Hee Ann

Full Text Available To assess the serial changes of de novo coronary lesions treated with paclitaxel-coated balloon (PCB using intravascular ultrasound virtual histology (IVUS-VH and fractional flow reserve (FFR.This prospective observational study enrolled 27 patients with coronary artery disease treated with PCB who underwent coronary angiography, IVUS-VH and FFR before, immediately after intervention and at 9 months. 28 de novo lesions were successfully treated with PCB. Angiographic late luminal loss was 0.02 ± 0.27 mm. Mean vessel and lumen areas showed increase at 9 months (12.0 ± 3.5 mm(2 to 13.2 ± 3.9 mm(2, p <0.001; and 5.4 ± 1.2 mm(2 to 6.5 ± 1.8 mm(2, p <0.001, respectively. Although mean plaque area was unchanged (6.6 ± 2.6 mm2 to 6.6 ± 2.4 mm(2, p = 0.269, percent atheroma volume decreased significantly (53.4 ± 7.9% to 49.5 ± 6.4%, p = 0.002. The proportion of plaque compositions including fibrous, fibrofatty, dense calcium and necrotic core by IVUS-VH was unchanged at 9 months. The FFR of the treated lesion was 0.71 ± 0.13 pre-procedure, 0.87 ± 0.06 post-procedure and 0.84 ± 0.06 at follow-up.De novo coronary lesions treated with PCB showed persistent anatomical and physiological patency with plaque redistribution and vessel remodeling without chronic elastic recoil or plaque compositional change during follow-up.

Relationship between quantitative measurement of Porphyromonas gingivalis on dental plaque with periodontal status of patients with coronary heart disease

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Dwiyanti, Stephani; Soeroso, Yuniarti; Sunarto, Hari; Radi, Basuni

2017-02-01

Coronary heart disease is a narrowing of coronary artery due to plaque build-up. [1] Chronic periodontitis increases risk of cardiovascular disease. P.gingivalis is linked to both diseases. Objective: to analyse quantitative difference of P.gingivalis on dental plaque and its relationship with periodontal status of CHD patient and control. Methods: Periodontal status of 66 CHD patient and 40 control was checked. Subgingival plaque was isolated and P.gingivalis was measured using real-time PCR. Result: P.gingivalis of CHD patient differs from control. P.gingivalis is linked to pocket depth of CHD patient. Conclusion: P.gingivalis count of CHD patient is higher than control. P.gingivalis count is not linked to any periodontal status, except for pocket depth of CHD patient.

Atherectomy devices: technology update

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Akkus NI

2014-12-01

Full Text Available Nuri I Akkus,1 Abdulrahman Abdulbaki,1 Enrique Jimenez,2 Neeraj Tandon2 1Department of Cardiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA; 2Department of Cardiology, Overton Brooks VA Medical Center, Shreveport, LA, USA Abstract: Atherectomy is a procedure which is performed to remove atherosclerotic plaque from diseased arteries. Atherosclerotic plaques are localized in either coronary or peripheral arterial vasculature and may have different characteristics depending on the texture of the plaque. Atherectomy has been used effectively in treatment of both coronary and peripheral arterial disease. Atherectomy devices are designed differently to either cut, shave, sand, or vaporize these plaques and have different indications. In this article, current atherectomy devices are reviewed. Keywords: coronary artery disease, peripheral arterial disease

Relationships of elevated systemic pentraxin-3 levels with high-risk coronary plaque components and impaired myocardial perfusion after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

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Kimura, Shigeki; Inagaki, Hiroshi; Haraguchi, Go; Sugiyama, Tomoyo; Miyazaki, Toru; Hatano, Yu; Yoshikawa, Shunji; Ashikaga, Takashi; Isobe, Mitsuaki

2014-01-01

We aimed to assess the relationships of pentraxin-3 (PTX3) with coronary plaque components and myocardial perfusion after percutaneous coronary intervention (PCI) in order to clarify the mechanisms underlying the prognostic function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients. We enrolled 75 STEMI patients who underwent pre-PCI virtual histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI PTX3 level with coronary plaque components and post-PCI myocardial blush grade (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median ≥3.79ng/ml) had higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%, P2 on admission (hazard ratio, 5.356; 95% CI, 1.409-20.359; P=0.014) as independent predictors of adverse cardiac events during follow-up. Systemic pre-PCI PTX3 was associated with high-risk plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a reliable predictor of outcome in STEMI patients.

IAP survivin regulates atherosclerotic macrophage survival

NARCIS (Netherlands)

Blanc-Brude, Olivier P.; Teissier, Elisabeth; Castier, Yves; Lesèche, Guy; Bijnens, Ann-Pascal; Daemen, Mat; Staels, Bart; Mallat, Ziad; Tedgui, Alain

2007-01-01

Inflammatory macrophage apoptosis is critical to atherosclerotic plaque formation, but its mechanisms remain enigmatic. We hypothesized that inhibitor of apoptosis protein (IAP) survivin regulates macrophage death in atherosclerosis. Western blot analysis revealed discrete survivin expression in

Correlation of atherosclerotic changes in peripheral arteries with pathological involvement of aortic arch in coronary bypass patients

Directory of Open Access Journals (Sweden)

Eshraghi N

2010-10-01

Full Text Available "nBackground: A correlation between coronary artery disease (CAD and atherosclerosis of peripheral arteries and the determination of noninvasive indexes for its existence and extent have been sought by many researchers. Some studies report that the intima-media thickness (IMT of peripheral arteries could play this role. This study evaluated the correlation between the IMTs of common carotid and common femoral arteries and the degree of atherosclerosis in aortic arch and to evaluate the severity of CAD in candidates of coronary artery bypass grafting (CABG."n "nMethods: In a cross-sectional analytic-descriptive study, The severity of CAD, the grade of atherosclerosis of the aortic arch, and the IMTs of the common carotid and common femoral arteries were determined."n "nResults: There was a significant weak positive correlation between the IMT of common carotid artery (ρ = 0.193, p = 0.039 and common femoral artery (ρ = 0.206, p = 0.028 with the number of involved carotid vessels; the mean of these two parameters was not significantly different between the three CAD groups. There was not any significant relation between the IMTs of common carotid and common femoral arteries with the severity of atherosclerosis in the aortic arch too. There was not any significant relation between the presences of atherosclerotic plaque in the common carotid or the common femoral arteries with the severity of CAD. The severe atherosclerosis of the aortic arch was significantly higher in patients with three vessel disease."n "nConclusion: According to our results, the IMTs of common carotid and/or common femoral arteries may increase with the severity of CAD; however, these parameters are not a surrogate for predicting the CAD severity.

Multicontrast-weighted magnetic resonance imaging of atherosclerotic plaques at 3.0 and 1.5 Tesla: ex-vivo comparison with histopathologic correlation

International Nuclear Information System (INIS)

Koops, Andreas; Ittrich, Harald; Priest, Andrew; Stork, Alexander; Adam, Gerhard; Weber, Christoph; Petri, Susan; Lockemann, Ute

2007-01-01

The purpose was to analyze magnetic resonance (MR) plaque imaging at 3.0 Tesla and 1.5 Tesla in correlation with histopathology. MR imaging (MRI) of the abdominal aorta and femoral artery was performed on seven corpses using T1-weighted, T2-weighted, and PD-weighted sequences at 3.0 and 1.5 Tesla. Cross-sectional images at the branching of the inferior mesenteric artery and the profunda femoris were rated with respect to image quality. Corresponding cross sections of the imaged vessels were obtained at autopsy. The atherosclerotic plaques in the histological slides and MR images were classified according to the American Heart Association (AHA) and analyzed for differences. MRI at 3.0 Tesla offered superior depiction of arterial wall composition in all contrast weightings, rated best for T2-weighted images. Comparing for field strength, the highest differences were observed in T1-weighted and T2-weighted techniques (both P≤0.001), with still significant differences in PD-weighted sequence (P≤0.005). The majority of plaques were histologically classified as calcified plaques. In up to 21% of the cases, MRI at both field strengths detected signal loss characteristic of calcification although calcified plaque was absent in histology. MRI at 3.0 Tesla offers superior plaque imaging quality compared with 1.5 Tesla, but further work is necessary to determine whether this translates in superior diagnostic accuracy. (orig.)

Near-Infrared Spectroscopy Enhances Intravascular Ultrasound Assessment of Vulnerable Coronary Plaque: A Combined Pathological and In Vivo Study.

Science.gov (United States)

Puri, Rishi; Madder, Ryan D; Madden, Sean P; Sum, Stephen T; Wolski, Kathy; Muller, James E; Andrews, Jordan; King, Karilane L; Kataoka, Yu; Uno, Kiyoko; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Virmani, Renu; Maehara, Akiko; Mintz, Gary S; Nicholls, Stephen J

2015-11-01

Pathological studies demonstrate the dual significance of plaque burden (PB) and lipid composition for mediating coronary plaque vulnerability. We evaluated relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries. Ex vivo coronary NIRS and IVUS imaging was performed through blood in 116 coronary arteries of 51 autopsied hearts, followed by 2-mm block sectioning (n=2070) and histological grading according to modified American Heart Association criteria. Lesions were defined as the most heavily diseased 2-mm block per imaged artery on IVUS. IVUS-derived PB and NIRS-derived lipid core burden index (LCBI) of each block and lesion were analyzed. Block-level analysis demonstrated significant trends of increasing PB and LCBI across more complex atheroma (Ptrend <0.001 for both LCBI and PB). Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (Ptrend <0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI, and remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB+LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, P=0.028 versus PB; net-reclassification index 43%, P=0.003), whereas further adding remodeling index did not (c index 0.80, P=0.27 versus PB+LCBI). In vivo comparisons of 43 age- and sex-matched patients (to the autopsy cohort) undergoing combined NIRS-IVUS coronary imaging yielded similar associations to those demonstrated ex vivo. Adding NIRS to conventional IVUS-derived PB imaging significantly improves the ability to detect more active, potentially vulnerable coronary atheroma. © 2015 American Heart Association, Inc.

Quantification of plaque area and characterization of plaque biochemical composition with atherosclerosis progression in ApoE/LDLR(-/-) mice by FT-IR imaging.

Science.gov (United States)

Wrobel, Tomasz P; Mateuszuk, Lukasz; Kostogrys, Renata B; Chlopicki, Stefan; Baranska, Malgorzata

2013-11-07

In this work the quantitative determination of atherosclerotic lesion area (ApoE/LDLR(-/-) mice) by FT-IR imaging is presented and validated by comparison with atherosclerotic lesion area determination by classic Oil Red O staining. Cluster analysis of FT-IR-based measurements in the 2800-3025 cm(-1) range allowed for quantitative analysis of the atherosclerosis plaque area, the results of which were highly correlated with those of Oil Red O histological staining (R(2) = 0.935). Moreover, a specific class obtained from a second cluster analysis of the aortic cross-section samples at different stages of disease progression (3, 4 and 6 months old) seemed to represent the macrophages (CD68) area within the atherosclerotic plaque.

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.

Localization of Coronary High-Intensity Signals on T1-Weighted MR Imaging: Relation to Plaque Morphology and Clinical Severity of Angina Pectoris.

Science.gov (United States)

Matsumoto, Kenji; Ehara, Shoichi; Hasegawa, Takao; Sakaguchi, Mikumo; Otsuka, Kenichiro; Yoshikawa, Junichi; Shimada, Kenei

2015-10-01

This study sought to investigate the relationship between localization of high-intensity signals (HISs) on T1-weighted imaging (T1WI) with the noncontrast magnetic resonance technique and plaque morphology detected on optical coherence tomography, and the clinical severity of angina pectoris. Since the introduction of the T1WI noncontrast magnetic resonance technique for plaque imaging, some groups have reported that HISs in the coronary artery on T1WI are associated with a vulnerable morphology and future cardiac events. However, the association between the localization of HISs, such as coronary intrawall or intraluminal, and plaque morphology has not been investigated. One hundred lesions with either stable or unstable angina were included and divided into 3 groups according to the following criteria using T1WI. First, the plaques with the ratio between the signal intensities of coronary plaque and cardiac muscle ≤1.0 were classified as non-HISs (n = 39). Then, HISs with the ratio between the signal intensities of coronary plaque and cardiac muscle >1.0 were classified into 2 types by using cross-sectional T1WI. Those localized within the coronary wall when the lumen was identified were defined as intrawall HISs (n = 37), whereas those occupying the lumen when the lumen was not, or even if only partly, identified, were defined as intraluminal HISs (n = 24). Multivariate analysis revealed that intrawall HISs were associated with macrophage accumulation and the absence of calcification assessed by using optical coherence tomography. In contrast, thrombus and intimal vasculature were independent factors associated with intraluminal HISs. Furthermore, 50% of patients with intraluminal HISs experienced rest angina, such as Braunwald class II or III. This study shows that intrawall and intraluminal HISs on T1WI in patients with angina are related to the different types of vulnerable plaque morphology and the clinical severity. Copyright © 2015 American College of

Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease.

Directory of Open Access Journals (Sweden)

Juan A Rodriguez-Feo

Full Text Available Caveolin-1 (Cav-1 is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target

First experiences with model based iterative reconstructions influence on quantitative plaque volume and intensity measurements in coronary computed tomography angiography

DEFF Research Database (Denmark)

Precht, Helle; Kitslaar, Pieter H.; Broersen, Alexander

2017-01-01

Purpose: Investigate the influence of adaptive statistical iterative reconstruction (ASIR) and the model- based IR (Veo) reconstruction algorithm in coronary computed tomography angiography (CCTA) im- ages on quantitative measurements in coronary arteries for plaque volumes and intensities. Methods...

Myocardial Bridges and their Relationship to the Anterior Interventricular Branch of the Left Coronary Artery

Directory of Open Access Journals (Sweden)

Lima Vanildo Júnior de Melo

2002-01-01

Full Text Available OBJECTIVE: To analyze the relationship between myocardial bridges and the anterior interventricular branch (anterior descending of the left coronary artery. METHODS: The study was carried out with postmortem material, and methods of dissection and observation were used. We assessed the perimeter of the anterior interventricular branch of the left coronary artery using a pachymeter, calculated its proximal and distal diameters in relation to the myocardial bridge, and also its diameter under the myocardial bridge in 30 hearts. We also observed the position of the myocardial bridge in relation to the origin of the anterior interventricular branch. RESULTS: The diameters of the anterior interventricular branch were as follows: the mean proximal diameter was 2.76±0.76 mm; the mean diameter under the myocardial bridge was 2.08±0.54 mm; and the mean distal diameter was 1.98±0.59 mm. In 33.33% (10/30 of the cases, the diameter of the anterior interventricular branch under the myocardial bridge was lower than the diameter of the anterior interventricular branch distal to the myocardial bridge. In 3.33% (1/30 of the cases, an atherosclerotic plaque was found in the segment under the myocardial bridge. The myocardial bridge was located in the middle third of the anterior interventricular branch in 86.66% (26/30 of the cases. CONCLUSION: Myocardial bridges are more frequently found in the middle third of the anterior interventricular branch of the left coronary artery. The diameter of the anterior interventricular branch of the left coronary artery under the myocardial bridge may be smaller than after the bridge. Myocardial bridges may not provide protection against the formation of atherosclerotic plaque inside the anterior interventricular branch of the left coronary artery.

Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions

NARCIS (Netherlands)

D.C. MacLeod (Donald); B.H. Strauss (Bradley); J. Escaned (Javier); V.A.W.M. Umans (Victor); R-J. van Suylen (Robert-Jan); A. Verkerk (Anton); P.J. de Feyter (Pim); P.W.J.C. Serruys (Patrick); M. de Jong (Marcel)

1994-01-01

textabstractOBJECTIVES. The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND. Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of

Multidetector row computed tomography may accurately estimate plaque vulnerability. Does MDCT accurately estimate plaque vulnerability? (Pro)

International Nuclear Information System (INIS)

Komatsu, Sei; Imai, Atsuko; Kodama, Kazuhisa

2011-01-01

Over the past decade, multidetector row computed tomography (MDCT) has become the most reliable and established of the noninvasive examination techniques for detecting coronary heart disease. Now MDCT is chasing intravascular ultrasound (IVUS) in terms of spatial resolution. Among the components of vulnerable plaque, MDCT may detect lipid-rich plaque, the lipid pool, and calcified spots using computed tomography number. Plaque components are detected by MDCT with high accuracy compared with IVUS and angioscopy when assessing vulnerable plaque. The TWINS study and TOGETHAR trial demonstrated that angioscopic loss of yellow color occurred independently of volumetric plaque change by statin therapy. These 2 studies showed that plaque stabilization and regression reflect independent processes mediated by different mechanisms and time course. Noncalcified plaque and/or low-density plaque was found to be the strongest predictor of cardiac events, regardless of lesion severity, and act as a potential marker of plaque vulnerability. MDCT may be an effective tool for early triage of patients with chest pain who have a normal electrocardiogram (ECG) and cardiac enzymes in the emergency department. MDCT has the potential ability to analyze coronary plaque quantitatively and qualitatively if some problems are resolved. MDCT may become an essential tool for detecting and preventing coronary artery disease in the future. (author)

Non-calcified coronary plaque volume inversely related to CD4(+) T-cell count in HIV infection.

Science.gov (United States)

Duarte, Horacio; Matta, Jatin R; Muldoon, Nancy; Masur, Henry; Hadigan, Colleen; Gharib, Ahmed M

2012-01-01

Non-calcified coronary artery plaque (NCAP) might be an important predictor of cardiovascular events; however, few studies have directly measured NCAP in HIV-infected individuals. We completed a prospective cross-sectional evaluation of NCAP and coronary calcium scores using computed tomography angiography in HIV-infected patients (n=26) without known coronary artery disease (CAD), but who had one or more CAD risk factor(s), and compared them with controls matched on age, race, sex, body mass index and Framingham Risk Score (n=26). There was no difference in coronary calcium scores (114 ± 218 versus 124 ± 298; P=0.89) or NCAP volume (65 ± 86 mm(3) versus 63 ± 82 mm(3); P=0.38) between HIV-infected patients and controls, respectively. Among HIV-infected patients, lower CD4(+) T-cell count was associated with increased NCAP volume (r=-0.52, P=0.006). The CD4(+) T-cell count remained a significant predictor of NCAP in a multivariate analysis that adjusted for age and duration of antiretroviral therapy. Plaque burden is similar between HIV-infected and uninfected individuals when matched on traditional CAD risk factors; however, immune function might mediate the development of atherosclerosis in HIV infection.

Standard deviation of carotid young's modulus and presence or absence of plaque improves prediction of coronary heart disease risk.

Science.gov (United States)

Niu, Lili; Zhang, Yanling; Qian, Ming; Xiao, Yang; Meng, Long; Zheng, Rongqin; Zheng, Hairong

2017-11-01

The stiffness of large arteries and the presence or absence of plaque are associated with coronary heart disease (CHD). Because arterial walls are biologically heterogeneous, the standard deviation of Young's modulus (YM-std) of the large arteries may better predict coronary atherosclerosis. However, the role of YM-std in the occurrence of coronary events has not been addressed so far. Therefore, this study investigated whether the carotid YM-std and the presence or absence of plaque improved CHD risk prediction. One hundred and three patients with CHD (age 66 ± 11 years) and 107 patients at high risk of atherosclerosis (age 61 ± 7 years) were recruited. Carotid YM was measured by the vessel texture matching method, and YM-std was calculated. Carotid intima-media thickness was measured by the MyLab 90 ultrasound Platform employed dedicated software RF-tracking technology. In logistic regression analysis, YM-std (OR = 1·010; 95% CI = 1·003-1·016), carotid plaque (OR = 16·759; 95% CI = 3·719-75·533) and YM-std plus plaque (OR = 0·989; 95% CI = 0·981-0·997) were independent predictors of CHD. The traditional risk factors (TRF) plus YM-std plus plaque model showed a significant improvement in area under the receiver-operating characteristic curve (AUC), which increased from 0·717 (TRF only) to 0·777 (95% CI for the difference in adjusted AUC: 0·010-0·110). Carotid YM-std is a powerful independent predictor of CHD. Adding plaque and YM-std to TRF improves CHD risk prediction. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Pseudomonas aeruginosa Microcolonies in Coronary Thrombi from Patients with ST-Segment Elevation Myocardial Infarction

DEFF Research Database (Denmark)

Hansen, Gorm Mørk; Belstrøm, Daniel; Nilsson, Carl Martin Peter

2016-01-01

Chronic infection is associated with an increased risk of atherothrombotic disease and direct bacterial infection of arteries has been suggested to contribute to the development of unstable atherosclerotic plaques. In this study, we examined coronary thrombi obtained in vivo from patients with ST......-segment elevation myocardial infarction (STEMI) for the presence of bacterial DNA and bacteria. Aspirated coronary thrombi from 22 patients with STEMI were collected during primary percutaneous coronary intervention and arterial blood control samples were drawn from radial or femoral artery sheaths. Analyses were...... performed using 16S polymerase chain reaction and with next-generation sequencing to determine bacterial taxonomic classification. In selected thrombi with the highest relative abundance of Pseudomonas aeruginosa DNA, peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) with universal...

2-Chlorohexadecanal and 2-chlorohexadecanoic acid induce COX-2 expression in human coronary artery endothelial cells

OpenAIRE

Messner, Maria C.; Albert, Carolyn J.; Ford, David A.

2008-01-01

2-Chlorohexadecanal (2-ClHDA), a 16-carbon chain chlorinated fatty aldehyde that is produced by reactive chlorinating species attack of plasmalogens, is elevated in atherosclerotic plaques, infarcted myocardium, and activated leukocytes. We tested the hypothesis that 2-ClHDA and its metabolites, 2-chlorohexadecanoic acid (2-ClHA) and 2-chlorohexadecanol (2-ClHOH), induce COX-2 expression in human coronary artery endothelial cells (HCAEC). COX-2 protein expression increased in response to 2-Cl...

Vulnerable plaque detection: The role of 18-fluorine ...

African Journals Online (AJOL)

Positron emission tomography computed tomography (PET-CT) is a combined functional and structural multi modality imaging tool that can be utilized to detect vulnerable and atherosclerotic plaques. In this study we observe the prevalence of active and calcified plaques in selected arteries during whole-body 18F-FDG ...

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

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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.

Variability and accuracy of coronary CT angiography including use of iterative reconstruction algorithms for plaque burden assessment as compared with intravascular ultrasound - an ex vivo study

Energy Technology Data Exchange (ETDEWEB)

Stolzmann, Paul [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Schlett, Christopher L.; Maurovich-Horvat, Pal; Scheffel, Hans; Engel, Leif-Christopher; Karolyi, Mihaly; Hoffmann, Udo [Massachusetts General Hospital and Harvard Medical School, Cardiac MR PET CT Program, Boston, MA (United States); Maehara, Akiko; Ma, Shixin; Mintz, Gary S. [Columbia University Medical Center, Cardiovascular Research Foundation, New York, NY (United States)

2012-10-15

To systematically assess inter-technique and inter-/intra-reader variability of coronary CT angiography (CTA) to measure plaque burden compared with intravascular ultrasound (IVUS) and to determine whether iterative reconstruction algorithms affect variability. IVUS and CTA data were acquired from nine human coronary arteries ex vivo. CT images were reconstructed using filtered back projection (FBPR) and iterative reconstruction algorithms: adaptive-statistical (ASIR) and model-based (MBIR). After co-registration of 284 cross-sections between IVUS and CTA, two readers manually delineated the cross-sectional plaque area in all images presented in random order. Average plaque burden by IVUS was 63.7 {+-} 10.7% and correlated significantly with all CTA measurements (r = 0.45-0.52; P < 0.001), while CTA overestimated the burden by 10 {+-} 10%. There were no significant differences among FBPR, ASIR and MBIR (P > 0.05). Increased overestimation was associated with smaller plaques, eccentricity and calcification (P < 0.001). Reproducibility of plaque burden by CTA and IVUS datasets was excellent with a low mean intra-/inter-reader variability of <1/<4% for CTA and <0.5/<1% for IVUS respectively (P < 0.05) with no significant difference between CT reconstruction algorithms (P > 0.05). In ex vivo coronary arteries, plaque burden by coronary CTA had extremely low inter-/intra-reader variability and correlated significantly with IVUS measurements. Accuracy as well as reader reliability were independent of CT image reconstruction algorithm. (orig.)

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

International Nuclear Information System (INIS)

Gabriels, Karen; Hoving, Saske; Gijbels, Marion J.; Pol, Jeffrey F.; Poele, Johannes A. te; Biessen, Erik A.; Daemen, Mat J.; Stewart, Fiona A.; Heeneman, Sylvia

2014-01-01

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

Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease.

Science.gov (United States)

Vrtovec, Matjaz; Anzic, Ajda; Zupan, Irena Preloznik; Zaletel, Katja; Blinc, Ales

2017-06-01

Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], β- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p 160, indicating high cardiovascular risk, not predicted by the Framingham equation.

Imaging unstable plaque

International Nuclear Information System (INIS)

SRIRANJAN, Rouchelle S.; TARKIN, Jason M.; RUDD, James H.; EVANS, Nicholas R.; CHOWDHURY, Mohammed M.

2016-01-01

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

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.

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

Science.gov (United States)

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

2007-12-01

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

Contrast-enhanced magnetic resonance imaging for the detection of ruptured coronary plaques in patients with acute myocardial infarction.

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Christian H P Jansen

Full Text Available X-ray coronary angiography (XCA is the current gold standard for the assessment of lumen encroaching coronary stenosis but XCA does not allow for early detection of rupture-prone vulnerable plaques, which are thought to be the precursor lesions of most acute myocardial infarctions (AMI and sudden death. The aim of this study was to investigate the potential of delayed contrast-enhanced magnetic resonance coronary vessel wall imaging (CE-MRCVI for the detection of culprit lesions in the coronary arteries.16 patients (13 male, age 61.9±8.6 years presenting with sub-acute MI underwent CE-MRCVI within 24-72h prior to invasive XCA. CE-MRCVI was performed using a T1-weighted 3D gradient echo inversion recovery sequence (3D IR TFE 40±4 minutes following the administration of 0.2 mmol/kg gadolinium-diethylenetriamine-pentaacetic acid (DTPA on a 3T MRI scanner equipped with a 32-channel cardiac coil.14 patients were found to have culprit lesions (7x LAD, 1xLCX, 6xRCA as identified by XCA. Quantitative CE-MRCVI correctly identified the culprit lesion location with a sensitivity of 79% and excluded culprit lesion formation with a specificity of 99%. The contrast to noise ratio (CNR of culprit lesions (9.7±4.1 significantly exceeded CNR values of segments without culprit lesions (2.9±1.9, p<0.001.CE-MRCVI allows the selective visualization of culprit lesions in patients immediately after myocardial infarction (MI. The pronounced contrast uptake in ruptured plaques may represent a surrogate biomarker of plaque activity and/or vulnerability.

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

OpenAIRE

Kathiresan, Sekar; Reilly, Muredach; Samani, Nilesh; Schunkert, Heribert; Erdmann, Jeanette; Moll, Frans; Boerwinkle, Eric; Hall, Anne; Hengstenberg, Christian; König, Inke; Laaksonen, Reijo; McPherson, Ruth; Thompson, John; Thorsteinsdottir, Unnur; Ziegler, Andreas

2011-01-01

textabstractBackground: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study withi...

High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined 18F-FDG PET/MR imaging

International Nuclear Information System (INIS)

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

2016-01-01

The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and 18 F-fluoro-deoxyglucose positron emission tomography ( 18 F-FDG PET) imaging. Carotid arteries were imaged 150 min after injection of 18 F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. 18 F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher 18 F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher 18 F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. Morphological and biological features of high-risk plaques can be detected with 18 F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal

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

Science.gov (United States)

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

2017-08-01

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

Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease

Science.gov (United States)

Vrtovec, Matjaz; Anzic, Ajda; Zupan, Irena Preloznik; Zaletel, Katja

2017-01-01

Abstract Background Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. Patients and methods 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. Results No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], β- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p 160, indicating high cardiovascular risk, not predicted by the Framingham equation. PMID:28740456

High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined {sup 18}F-FDG PET/MR imaging

Energy Technology Data Exchange (ETDEWEB)

Hyafil, Fabien [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Bichat University Hospital, Department of Nuclear Medicine, Paris (France); Schindler, Andreas; Obenhuber, Tilman; Saam, Tobias [Ludwig Maximilians University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Sepp, Dominik; Hoehn, Sabine; Poppert, Holger [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Bayer-Karpinska, Anna [Ludwig Maximilians University Hospital Munich, Institute for Stroke and Dementia Research, Munich (Germany); Boeckh-Behrens, Tobias [Technische Universitaet Muenchen, Department of Neuroradiology, Klinikum Rechts der Isar, Munich (Germany); Hacker, Marcus [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Nekolla, Stephan G. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Partner Site Munich Heart Alliance, German Centre for Cardiovascular Research (DZHK), Munich (Germany); Rominger, Axel [Ludwig Maximilians University Hospital Munich, Department of Nuclear Medicine, Munich (Germany); Dichgans, Martin [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Munich Cluster of Systems Neurology (SyNergy), Munich (Germany); Schwaiger, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

2016-02-15

The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and {sup 18}F-fluoro-deoxyglucose positron emission tomography ({sup 18}F-FDG PET) imaging. Carotid arteries were imaged 150 min after injection of {sup 18}F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. {sup 18}F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher {sup 18}F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher {sup 18}F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. Morphological and biological features of high-risk plaques can be detected with {sup 18}F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral

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

Directory of Open Access Journals (Sweden)

Jami L. Johnson

2018-03-01

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

Collagen turnover in arterial disease

NARCIS (Netherlands)

Sluijter, J.P.G.

2004-01-01

Increased atherosclerotic plaque formation can lead to lumen reduction and finally to lumen obstruction. Percutaneous transluminal angioplasty (PTA) or balloon angioplasty (dilation) are approaches generally used to treat coronary, but also peripheral atherosclerotic disease. Their goal is to

Control of atherosclerotic plaque vulnerability: insights from transgenic mice

NARCIS (Netherlands)

Heeneman, Sylvia; Lutgens, Esther; Schapira, Kitty B.; Daemen, Mat J. A. P.; Biessen, Erik A. L.

2008-01-01

Atherosclerosis is a complex, progressive disease of the large systemic arteries. This multi-factorial disease is characterized by accumulation of lipids, cells and extracellular matrix in the vessel wall. The quest to unravel the molecular mechanisms leading to progression of human atherosclerotic

Plaque Burden Influences Accurate Classification of Fibrous Cap Atheroma by In-Vivo Optical Coherence Tomography in a Porcine Model of Advanced Coronary Atherosclerosis

DEFF Research Database (Denmark)

Poulsen, Christian B; Pedrigi, Ryan M; Pareek, Nilesh

2018-01-01

AIMS: In-vivo validation of coronary optical coherence tomography (OCT) against histology and the effects of plaque burden (PB) on plaque classification remain unreported. We investigated this in a porcine model with human-like coronary atherosclerosis. METHODS AND RESULTS: Five female Yucatan D374...... a validated algorithm. Lesions were adjudicated using the Virmani classification and PB assessed from histology. OCT had a high sensitivity, but modest specificity (92.9% and 74.6%), for identifying fibrous cap atheroma (FCA). The reduced specificity for OCT was due to misclassification of plaques...... with histologically defined pathological intimal thickening (PIT) as FCA (46.1% of the frames with histological PIT were misclassified). PIT lesions misclassified as FCA by OCT had a statistically higher PB than in other OCT frames (median 32.0% versus 13.4%; p

COX-2 Gene Promoter Polymorphism and Coronary Artery Disease in Middle-Aged Men: The Helsinki Sudden Death Study

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Kati H. Huuskonen

2008-01-01

Full Text Available Cyclooxygenase (COX catalyzes formation of prostaglandins that contribute to the inflammation in atherosclerosis. Our objective was to study whether the functional C variant of the −765G→C polymorphism in the human COX-2 gene associates with the severity of coronary atherosclerosis measured at the coronary artery level. The Helsinki sudden death study autopsy material (n = 300 comprised of Finnish men who died suddenly. The area of atherosclerotic lesions in the coronary arteries was quantitated, and coronary narrowing was measured. The occurrence of myocardial infarction (MI was assessed. Genotyping was by restriction endonuclease analysis. Men carrying the minor C allele had larger areas of complicated lesions (P = .024 and a higher number of coronary arteries that had over 50% stenosis (P = .036 compared to men representing the common GG genotype. The COX-2 polymorphism was not associated with MI. Our data suggest that COX-2 may be involved in plaque growth.

Panax Notoginseng Saponins Promote Endothelial Progenitor Cell Mobilization and Attenuate Atherosclerotic Lesions in Apolipoprotein E Knockout Mice

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Ya Liu

2013-09-01

Full Text Available Background: Endothelial progenitor cells (EPCs derived from the bone marrow (BM play a key role in the homeostasis of vascular repair by enhanced reendothelialization. Panax notoginseng saponins (PNS, a highly valued traditional Chinese medicine, has been shown to reduce morbidity and mortality from coronary artery disease. The present research was designed to explore the contribution of progenitor cells to the progression of atherosclerotic plaques and the possible modulatory role of PNS in this process. Methods: PNS (60 or 120 mg/kg via intraperitoneal injection was administered over 8 weeks in apolipoprotein E knockout mice on an atherogenic diet. The sizes and histochemical alteration of atherosclerotic lesions and numbers of EPCs in BM and peripheral blood were analyzed. The expression of chemokine stromal cell-derived factor 1α (SDF-1α and its receptor, CXCR4, was monitored as well. Results: PNS significantly reduced the lesion area and intima-to-media ratio compared to vehicle treatment. PNS also augmented endothelialization and reduced the smooth muscle cell (SMCs content of the lesions. The number of c-kit and sca-1 double-positive progenitor cells and flk-1 and sca-1 double-positive progenitor cells were significantly increased in the BM and the peripheral blood of the PNS-treated groups. PNS treatment increased the plasma levels of SDF-1α and SCF as well as the BM levels of matrix metalloproteinase-9 (MMP-9. Moreover, the mRNA levels of SDF-1α and protein levels of CXCR4 were both increased in the BM of mice treated with PNS, while SDF-1α expression decreased. Conclusion: PNS reduce the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilization. SDF-1α-CXCR4 interactions and the possible modulatory role of PNS in this process may contribute to the increased progenitor cell mobilization.

Cell proliferation in the atherosclerotic plaques of cholesterol-fed rabbits