Types Of Atherosclerotic Plaques Research Articles

AHA classification of coronary and carotid atherosclerotic plaques by grating-based phase-contrast computed tomography.

To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria. Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated. A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5%), III in 18 (14.2%), IV/V in 38 (29.9%), VI in 16 (12.6%), VII in 34 (26.8%) and VIII in 9 (7.0%) cross-sections. Sensitivity, specificity and positive and negative predictive value were ≥0.88 for most analyzed plaque types with a good level of agreement (Cohen's kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p < 0.0001. These results indicate that gb-PCCT can reliably classify atherosclerotic plaques according to modified AHA criteria with excellent agreement to histopathology. • Different atherosclerotic plaque types display distinct morphological features in phase-contrast CT. • Phase-contrast CT can detect and differentiate AHA plaque types. • Calcifications caused streak artefacts and reduced sensitivity in type VI lesions. • Overall agreement was higher in carotid than in coronary arteries.

Simulated imaging of atherosclerotic & radiofrequency ablation lesions using phase subtraction.

Cardiovascular diseases are the main cause of death worldwide. Atherosclerosis and atrial fibrillation are structural and electrical pathophysiology, respectively, that can lead to acute events such as stroke or myocardial infarction. We used particle-based Monte Carlo methods to simulate X-ray phase imaging of atherosclerotic plaque types IV-VIII in the aorta, iliac, and coronary arteries. We also assessed scar lesion development in radiofrequency catheter ablation treatment of atrial fibrillation by simulating lesions 2, 5, 10, 30, and 60 days post-procedure. For both applications, we found high signal-to-noise and contrast-to-noise ratios in all lesions. These results suggest that X-ray phase imaging is a viable technique for non-invasive quantitative cardiovascular lesion characterization.

Error propagation in the characterization of atheromatic plaque types based on imaging

Imaging systems transmit and acquire signals and are subject to errors including: error sources, signal variations or possible calibration errors. These errors are included in all imaging systems for atherosclerosis and are propagated to methodologies implemented for the segmentation and characterization of atherosclerotic plaque. In this paper, we present a study for the propagation of imaging errors and image segmentation errors in plaque characterization methods applied to 2D vascular images. More specifically, the maximum error that can be propagated to the plaque characterization results is estimated, assuming worst-case scenarios. The proposed error propagation methodology is validated using methods applied to real datasets, obtained from intravascular imaging (IVUS) and optical coherence tomography (OCT) for coronary arteries, and magnetic resonance imaging (MRI) for carotid arteries. The plaque characterization methods have recently been presented in the literature and are able to detect the vessel borders, and characterize the atherosclerotic plaque types. Although, these methods have been extensively validated using as gold standard expert annotations, by applying the proposed error propagation methodology a more realistic validation is performed taking into account the effect of the border detection algorithms error and the image formation error into the final results. The Pearson's coefficient of the detected plaques has changed significantly when the method was applied to IVUS and OCT, while there was not any variation when the method was applied to MRI data.

Nanoparticle uptake by macrophages in vulnerable plaques for atherosclerosis diagnosis.

The composition of atherosclerotic (AS) plaques is crucial concerning rupture, thrombosis and clinical events. Two plaque types are distinguished: stable and vulnerable plaques. Vulnerable plaques are rich in inflammatory cells, mostly only M1 macrophages, and are highly susceptible to rupture. These plaques represent a high risk particularly with the standard invasive diagnosis by coronary angiography. So far there are no non-invasive low-risk clinical approaches available to detect and distinguish AS plaque types in vivo. The perspective review introduces a whole work-flow for a novel approach for non-invasive detection and classification of AS plaques using the diffusion reflection method with gold nanoparticle loaded macrophages in combination with flow and image cytometric analysis for quality assurance. Classical biophotonic methods for AS diagnosis are summarized. Phenotyping of monocytes and macrophages are discussed for specific subset labelling by nanomaterials, as well as existing studies and first experimental proofs of concept for the novel approach are shown. In vitro and in vivo detection of NP loaded macrophages (MΦ). Different ways of MΦ labelling include (1) in vitro labelling in suspension (whole blood or buffy coat) or (2) labelling of short-term MΦ cultures with re-injection of MΦ-NP into the animal to detect migration of the cells in the plaques and (3) in vivo injection of NP into the organism.

Myosin light chain kinase inhibitor ML7 improves vascular endothelial dysfunction via tight junction regulation in a rabbit model of atherosclerosis.

Vascular endothelial dysfunction (VED) is an important factor in the initiation and development of atherosclerosis (AS). Previous studies have demonstrated that endothelial permeability is increased in diet-induced AS. However, the precise underlying mechanisms remain poorly understood. The present study aimed to analyze whether the myosin light chain kinase (MLCK) inhibitor ML7 is able to improve VED and AS by regulating the expression of the tight junction (TJ) proteins zona occludens (ZO)-1 and occludin via mechanisms involving MLCK and MLC phosphorylation in high-fat diet-fed rabbits. New Zealand white rabbits were randomly divided into three groups: Control group, AS group and ML7 group. The rabbits were fed a standard diet (control group), a high-fat diet (AS group) or a high-fat diet supplemented with 1 mg/kg/day ML7 (ML7 group). After 12 weeks, endothelium-dependent relaxation and endothelium-independent relaxation were measured using high-frequency ultrasound. Administration of a high-fat diet significantly increased the levels of serum lipids and inflammatory markers in the rabbits in the AS group, as compared with those in the rabbits in the control group. Furthermore, a high-fat diet contributed to the formation of a typical atherosclerotic plaque, as well as an increase in endothelial permeability and VED. These symptoms of AS were significantly improved following treatment with ML7, as demonstrated in the ML7 group. Hematoxylin & eosin and immunohistochemical staining indicated that ML7 was able to decrease the expression of MLCK and MLC phosphorylation in the arterial wall of rabbits fed a high-fat diet. A similar change was observed for the TJ proteins ZO-1 and occludin. In addition, western blot analysis demonstrated that ML7 increased the expression levels of occludin in the precipitate, but reduced its expression in the supernatant of lysed aortas. These results indicated that occludin, which is a dynamic protein at the TJ, is associated with remodeling from cell membrane to cytoplasm. The present study was the first, to the best of our knowledge, to indicate that ML7 may ameliorate VED and AS by regulating the TJ proteins ZO-1 and occludin via mechanisms involving MLCK and MLC phosphorylation.

Histomorphological evaluation of atherosclerotic lesions in patients with peripheral artery occlusive disease

PurposePeripheral arterial occlusive disease (PAOD) is mainly caused by atherosclerosis of the vessel wall. These pathological changes are classified into different stages and are well described for carotid and coronary vessels, but not for PAOD. The aim of our study was to analyze plaque morphology of femoral arteries in patients with intermittent claudication and critical limb ischemia. Patients and methodsIn this retrospective study 85 atherosclerotic plaques (common and superficial femoral artery) of 71 patients with a clinical symptomatic PAOD were analyzed, by histology (01/2009–07/2010). Atherosclerotic lesions were classified according to Stary (type I–VIII). For further characterization, plaques were evaluated for the presence of collagen, elastin, calcifications, smooth muscle cells, macrophages, leucocytes, and cellularity. ResultsThe majority (91%) of atherosclerotic lesions were of advanced types according to Stary (V–VII). Atherosclerotic lesion type VI was associated with significant higher amount of inflammatory cells in comparison to all other atherosclerotic plaque types (CD45: p<0.001; CD68: p=0.013). In addition, atherosclerotic plaques with a pronounced neovascularization contained a higher amount of CD45 (p=0.015; rho=0.273) and CD68 (p=0.016; rho=0.275) positive cells. ConclusionAtherosclerotic lesions of femoral arteries show similar morphological changes as coronary or carotid arteries. But inflammatory cells had a higher impact on plaque progression and destabilization than any other factor.

Macrophage content detection in an experimental rabbit model of atherosclerotic plaque by optical coherence tomography

To evaluate the feasibility of detecting macrophage content on atherosclerotic plaques by optical coherence tomography (OCT) technique. Thirty New Zealand white rabbits were equally divided into 3 groups at random: Control group (fed normal rabbit chow, n = 10); lipid diet group (fed regular chow supplemented with cholesterol, n = 10) and balloon injury+ lipid diet group (balloon catheter injury of the common carotid artery after 2 weeks lipid diet, n = 10). After 12 weeks, all rabbits underwent pharmacological triggering with Chinese Russell's viper venom (CRVV, 15 mg/kg, i.p.) and histamine (0.02 mg/kg, i.v.). Common carotid arteries were detected with OCT and the Movat pentachrome stain respectively. OCT and histological examination results were compared and the correlation was analyzed. The intra thickness measured by Movat pentachrome stain and by the OCT was (15.2 ± 0.9) µm and (20.2 ± 7.6) µm, the medial thickness was (434.2 ± 86.5) µm and (453.8 ± 87.2) µm, the plaque thickness was (330.2 ± 87.1) µm and (392.2 ± 134.5) µm, the fibrous cap thickness was (58.3 ± 5.6) µm and (61.2 ± 4.9) µm, respectively (all P > 0.05). The normalized standard deviation of the OCT signal (NSD) was compared with immunohistochemical detection. The OCT signal within the cap is relatively homogeneous for low macrophage density in high lipid diet group. For the raw OCT data, a correlation of r = 0.846 (P < 0.01) was found between OCT NSD and a CD68 area<10%, whereas for the base 10 logarithm OCT data, a correlation of r = 0.646 (P < 0.05) was found between OCT NSD and a CD68 area<10%. In balloon injury + high lipid diet group, the OCT signal within the cap was relatively heterogeneous for high macrophage content. For the raw OCT data, a correlation of r = 0.906 (P < 0.01) was found between OCT NSD and a CD68 area >10%, whereas for the base 10 logarithm OCT data, a correlation of r = 0.593 (P < 0.05) was found between OCT NSD and a CD68 area >10%. For the raw OCT signal NSD, a range of NSDs (7.12% to 7.35%) demonstrated 100% sensitivity and specificity (Kappa value 1.0) for differentiating caps containing >10% CD68 staining. For the base 10 logarithm OCT signal, NSD values ranging from 7.81% to 7.92% provided 70% sensitivity and 75% specificity (value 0.44) for identifying caps containing >10% CD68 staining. OCT is an effective tool to determine macrophage content in this model. OCT imaging can clearly visualize different types of atherosclerotic plaques and provide detailed information on plaque characteristics.

The roles of a novel inflammatory neopterin in subjects with coronary atherosclerotic heart disease

Coronary atherosclerotic heart disease (CHD) is currently regarded as a chronic inflammatory disease. The inflammatory cytokine neopterin (NP) is a new predictor of the stable type of atherosclerotic plaque, and this study focused on the relationship between neopterin, Gensini score and high-sensitivity C-reactive protein (Hs-CRP) to explore the important role of neopterin in patients with CHD. This study enrolled 176 patients into the control group and 266 patients into the experimental group. The Gensini score was used to assess the severity of the coronary lesions, enzyme-linked immunosorbent assays (ELISAs) were used to measure the serum NP level, and other indicators were assessed using a fully automatic biochemical analyzer. The data were analyzed using SPSS19.0 statistical software. The serum NP level was higher in the experimental group than in the control group (132.23±6.40ng/mL vs. 40.95±2.67ng/mL, P<0.001). Compared with the stable angina (SA) group, the serum NP level was significantly increased in the unstable angina (UA) group (135.99±12.45ng/mL) and the acute myocardial infarction (AMI) group (173.66±13.59ng/mL) (P<0.05). In addition, the serum NP level was positively correlated with the Gensini score (r=0.687, P<0.001) as well as with the level of Hs-CRP (r=0.190, P<0.001). The serum level of NP was significantly higher in patients with CHD and was positively correlated with the severity of CHD. Thus, NP may become a new indicator for the assessment of the inflammatory response in coronary atherosclerosis.

Vascular Pathology in the Extracranial Vertebral Arteries in Patients with Acute Ischemic Stroke

Introduction: Vascular pathology in the extracranial vertebral arteries remains among the possible causes in cryptogenic stroke. However, the diagnosis is challenged by the great variety in the anatomy of the vertebral arteries, clinical symptoms and difficulties in the radiological assessments. The aim of this study was to assess the prevalence of CT angiography (CTA)-detected pathological findings in the extracranial vertebral arteries in an acute stroke population and secondly to determine the frequency of posterior pathology as probable cause in patients with otherwise cryptogenic stroke. Method: The analysis was based on 657 consecutive patients with symptoms of acute stroke and a final diagnosis of ischemic stroke or transient ischemic attack. On admission, a noncontrast CT cerebrum and CTA were performed. A senior consultant neuroradiologist, blinded to clinical data, reviewed all CTA scans systematically, assessing the four segments of the extracranial vertebral arteries. First, the frequency of pathological findings including stenosis, plaques, dissection, kinked artery and coiling was assessed. Subsequently, we explored the extent of the pathological findings that were the most plausible causes of stroke, namely either a possible dissection or a kinked artery. Results: Findings in the extracranial vertebral arteries included significant stenosis (0.8%), atherosclerotic plaque types (3.8%), possible dissections (2.6%), kinked arteries (2.6%) and coiling (32.0%). Eighteen patients (2.8%) with pathological findings had an unknown cause of stroke, likely posterior symptoms and no clinical stroke symptoms from the anterior circuit. Of these, 3 cases were kinked arteries (0.5%) and 15 cases (2.3%) were possible dissections. Conclusion: We found that in approximately 3% of the study population, the most plausible cause of the cryptogenic strokes was due to a pathological finding in the posterior extracranial vertebral arteries, being either a possible dissection or a kinked artery. In general, posterior vascular pathology is not uncommon, and CTA is a useful modality in the detection of changes based on characteristics and locations of findings in the extracranial vertebral arteries. Ultrasound examination can be a useful supplementary tool in deciding the consequence of vascular findings on CTA.

Internal Mammary Artery Atherosclerosis: An Ultrastructural Study of Two Cases

Atherosclerosis of the internal mammary artery (IMA) is generally regarded as a rare (but existent) pathological entity with only a few cases reported in the most recent literature. The only study which to our knowledge has investigated the ultrastructural features of IMA atherosclerosis, demonstrate the presence of endothelial cells loss, defects of internal elastic lamina with no evidence of lipid accumulation. In the present study, we describe two cases of IMA atherosclerosis in which ultrastructural analysis revealed the presence of a typical atherosclerotic plaque morphology with infiltration of inflammatory cells, formation of intraplaque lipid pools, and accumulation of lipid-laden foam cells throughout the thickened intima, never described in this rare lesion before. Microscopically, the lesions were also characterized by intimal thickening, invagination of endothelial cells, migration of smooth muscle cells with splitting, fenestration and/or fragmentation of the elastic sheets. Our observations add new data to the scarce and contradictory literature and to this largely understudied vascular disorder.

Impact of gender on the density of intraplaque neovascularization: A quantitative contrast-enhanced ultrasound study

ObjectiveAtherosclerosis is the main underlying cause of the majority of cardiovascular events. Although cardiovascular diseases (CVD) are a major challenge in both males and females, gender specific differences in the prevalence of CVD have been observed. This may indicate that there are differences in the development of atherosclerosis between males and females. The presence of intraplaque neovessels (IPN) is an imaging marker for plaque vulnerability. The aim of this study was to investigate the impact of gender on IPN. MethodsA total of 159 patients with ≥1 cardiovascular risk factor were included in this prospective study (mean age 56.9 ± 8.7 years, 47% females). Patients had no symptoms of carotid atherosclerotic disease. All patients underwent a standard carotid ultrasound examination in conjunction with contrast-enhanced ultrasound (CEUS). The presence of atherosclerotic plaques was assessed according to the Mannheim consensus. IPN was assessed using a visual grading scale and semi-automated quantification software. ResultsSubclinical atherosclerosis was detected using standard carotid ultrasound and CEUS in 64 females (86%) and in 79 males (93%) (p = 0.177). The mean atherosclerotic plaque sizes were not significantly different (p = 0.068). Semi-automated quantification of IPN demonstrated that females had significant more IPN compared to males (p < 0.05). After adjustment for clinical variables this association remained significant (p < 0.05). ConclusionIn this population at increased risk for CVD, females had significantly more IPN compared to males. This suggests that the females had a more vulnerable atherosclerotic plaque type.

Miniature optical coherence tomography-ultrasound probe for automatically coregistered three-dimensional intracoronary imaging with real-time display

We have developed a novel miniature integrated optical coherence tomography (OCT)-intravascular ultrasound (IVUS) probe, with a 1.5-mm-long rigid part and 0.9-mm outer diameter, for real-time intracoronary imaging of atherosclerotic plaques and guiding of interventional procedures. By placing the OCT ball lens and IVUS transducer back-to-back at the same axial position, this probe can provide automatically coregistered, coaxial OCT-IVUS imaging. To demonstrate its real-time capability, three-dimensional OCT-IVUS imaging of a pig's coronary artery displaying in polar coordinates, as well as images of three major types of atherosclerotic plaques in human cadaver coronary segments, were obtained using this probe and our upgraded system. Histology validation is also presented.

Melatonin ameliorates vascular endothelial dysfunction, inflammation, and atherosclerosis by suppressing the TLR4/NF‐κB system in high‐fat‐fed rabbits

Vascular endothelial dysfunction (VED) and inflammation contribute to the initiation and progression of atherosclerosis. Melatonin (MLT) normalizes lipid profile, improves endothelial function, and possesses anti-inflammatory properties. However, the precise mechanisms are still unclear. This study investigated whether MLT could ameliorate VED, inflammation, and atherosclerosis by suppressing the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) system in high-fat-fed rabbits. Rabbits were randomly divided into three groups that received a standard diet (control group), high-cholesterol diet (atherosclerosis group), or high-cholesterol diet plus 10mg/kg/day MLT (MLT group) for 12wk. After treatment, high-fat diet significantly increased serum lipid and inflammatory markers in rabbits in atherosclerosis group compared with that in control group. In addition, high-fat diet also induced VED and typical atherosclerotic plaque formation and increased intima/media thickness ratio, which were significantly improved by MLT therapy as demonstrated in MLT group. Histological and immunoblot analysis further showed that high-fat diet enhanced the expressions of TLR4, myeloid differentiation primary response protein (MyD88), and NF-κB p65, but decreased inhibitor of NF-κB (IκB) expression. By contrast, MLT therapy decreased the expressions of TLR4, MyD88, and NF-κB p65 and increased IκB expression. This study has demonstrated that MLT ameliorates lipid metabolism, VED, and inflammation and inhibits the progression of atherosclerosis in high-fat-fed rabbits. Moreover, our study indicates for the first time that suppression of the TLR4/NF-κB system in local vasculature with atherosclerotic damage is important for the protective effects of MLT.

Atorvastatin Inhibits the 5-Lipoxygenase Pathway and Expression of CCL3 to Alleviate Atherosclerotic Lesions in Atherosclerotic ApoE Knockout Mice

The 5-lipoxygenase (5-LO) pathway and the chemokine CCL3 are involved in the inflammatory processes of atherosclerosis. Statins have shown cholesterol-independent pleiotropic effects on antiimmune and antiinflammatory responses in atherosclerosis. We postulated that this effect may be associated with the 5-LO pathway and CCL3. ApoE knockout mice were randomized into control group (normal diet), atherosclerosis group (high-cholesterol diet), and atorvastatin group (high-cholesterol diet and atorvastatin). Sixteen weeks later, aortic roots were stained with hematoxylin and eosin. Total cholesterol and low-density lipoprotein cholesterol were measured by the enzymatic methods. The gene and protein expressions of 5-LO and CCL3 were detected separately through real-time reverse transcription polymerase chain reaction and western blotting analyses. The serum levels of leukotriene B4 and leukotriene D4 were measured by enzyme-linked immunosorbent assay. All mice have atherosclerotic plaques, mice in the control group have only tiny atherosclerotic plaques, but mice in the atherosclerosis group and atorvastatin group have typical atherosclerotic plaques. The corrected plaque areas (plaque area/luminal area) of the aortas of mice in the atorvastatin group were significantly decreased compared with those of the atherosclerosis group. The serum cholesterol levels of the atorvastatin group were not of significant difference compared with those of the atherosclerosis group. The gene and protein expressions of 5-LO and CCL3 in the aortas, as well as the serum levels of leukotriene B4 and leukotriene D4 in atorvastatin group, were markedly reduced compared with those of the atherosclerosis group. These data suggested that atorvastatin significantly alleviated atherosclerotic lesions by inhibiting the 5-LO pathway and down regulating the expression of CCL3 in ApoE-/- mice.

CD4+CD28− lymphocytes and cerebral ischaemic stroke. Part II: CD4+CD28− lymphocytes and carotid artery atherosclerotic plaque characteristics

Background and purposeCD4+CD28− lymphocytes can directly contribute to the instability of atherosclerotic plaque. This paper attempts to answer the question of the potential influence of the CD4+CD28− lymphocyte population on the ultrasound image of atherosclerotic plaque in the common carotid artery (CCA) wall. Material and methodsThe study involved a group of 109 patients, aged 45 to 65 years, including 42 patients with first-ever ischaemic stroke, experiencing symptoms resulting from disturbances of the anterior area of cerebral circulation, arterial hypertension and/or type 2 diabetes mellitus (group 1). Group 2 consisted of 34 patients with mentioned risk factors, without ischaemic stroke. The control group comprised 33 healthy individuals. The percentage of CD4+CD28− lymphocytes was assessed with flow cytometry. ResultsA significant difference in the incidence of heterogeneous plaques was noted between groups 1 and 3 (p = = 0.0023) as well as between group 2 and 3 (p = 0.0005), whereas groups 1 and 2 did not differ from each other. The proportion of CD4+CD28− lymphocytes was similar in groups 1 and 2 (p = 0.97), but it differed between groups 1 and 3 (p < 0.0001) and between groups 2 and 3 (p < 0.001). A correlation was found between the proportion of CD4+CD28− lymphocytes in the blood and the number of CCA atherosclerotic plaques (Rs = 0.191, p = 0.046). The proportion of CD4+CD28− lymphocytes in peripheral blood did not correlate with the ultrasound types of atherosclerotic plaques. No correlation between the proportion of CD4+CD28− lymphocytes and the area of atherosclerotic plaques was found. ConclusionsThe correlation between the proportion of CD4+CD28− lymphocytes and the number of atherosclerotic plaques within the CCA suggests that the cells are involved in the mechanism of carotid plaque formation. There is no proof of the involvement of the above-mentioned cells in the mechanism of plaque destabilization in those arteries.

Application of non-negative matrix factorization to multispectral FLIM data analysis

Existing methods of interpreting fluorescence lifetime imaging microscopy (FLIM) images are based on comparing the intensity and lifetime values at each pixel with those of known fluorophores. This method becomes unwieldy and subjective in many practical applications where there are several fluorescing species contributing to the bulk fluorescence signal, and even more so in the case of multispectral FLIM. Non-negative matrix factorization (NMF) is a multivariate data analysis technique aimed at extracting non-negative signatures of pure components and their non-negative abundances from an additive mixture of those components. In this paper, we present the application of NMF to multispectral time-domain FLIM data to obtain a new set of FLIM features (relative abundance of constituent fluorophores). These features are more intuitive and easier to interpret than the standard fluorescence intensity and lifetime values. The proposed approach, unlike several FLIM data analysis methods, is not limited by the number of constituent fluorescing species or their possibly complex decay dynamics. Moreover, the new set of FLIM features can be obtained by processing raw multispectral FLIM intensity data, thereby rendering time deconvolution unnecessary and resulting in lesser computational time and relaxed SNR requirements. The performance of the NMF method was validated on simulated and experimental multispectral time-domain FLIM data. The NMF features were also compared against the standard intensity and lifetime features, in terms of their ability to discriminate between different types of atherosclerotic plaques.

Activity of the Inflammatory Process in Different Types of Unstable Atherosclerotic Plaques

Inflammatory biomarkers and chemoattractants characteristic and important for different types (lipid; inflammatory erosive; degenerative necrotic) of unstable plaques in coronary arteries were identified and studied in male patients with coronary atherosclerosis without acute coronary syndrome we studied. Among the three types of unstable plaques, elevated concentrations of IL-1β, IL-6, IL-8, IL-18 and monocyte chemotactic protein-1 were characteristic of not only inflammatory erosive type, but also lipid type compared with degenerative necrotic type. Thus, intensification of the inflammatory process plays an important role in the development of not only inflammatory and destructive, but also of lipid type of unstable atherosclerotic plaques.

Urokinase receptor surface expression regulates monocyte migration and is associated with accelerated atherosclerosis

BackgroundThe urokinase receptor (uPAR) is a key regulator of pericellular proteolysis, cell adhesion and migration, all of which are fundamental processes in atherogenesis. We hypothesized that increased monocytic uPAR expression in circulation is associated with the formation and development of atherosclerosis. MethodsA total of 42 male apoE−/− mice were ramdonly divided into high-fat (HF) diet and normal diet (n=21 per group). The percentage of uPAR expressing monocytes (PUEM) and the expression of uPAR within different types of atherosclerotic plaques were measured at an interval of 3weeks from week 10 to week 16. In vitro, uPAR expression upon ox-LDL stimulation and the migration of monocytes were examined. ResultsPUEM in circulation was significantly higher in animals with HF diet compared with those having normal diet (p<0.03). The augmented levels of PUEM were associated with body weight, visceral fat weight and numbers of uPAR+macrophages within atherosclerotic lesions. Accumulation of uPAR+macrophages increased with the progression of atherosclerosis. Monocytes upon ox-LDL stimulation exhibited an increased uPAR expression and uPAR antibody markedly suppressed monocyte migration induced by monocyte chemotactic protein-1. uPAR modulated monocyte migration was accelerated by uPA and was suppressed by amino terminal fragment of uPA dependent. ConclusionsOver-expression of uPAR both in circulating monocytes and in atherosclerotic lesions is associated with the development of atherosclerotic plaques. uPAR and its interaction with uPA may contribute to enhanced monocyte migration. Thus, uPAR may be a novel target for prevention of uncontrolled monocyte recruitment in inflammatory atherogenic process.

Effects of Induction/Inhibition of Endogenous Heme Oxygenase-1 on Lipid Metabolism, Endothelial Function, and Atherosclerosis in Rabbits on a High Fat Diet

The heme oxygenase-1 (HO-1) / carbon monoxide (CO) system has been presumed as a therapeutic target for preventing atherosclerosis. However, the exact mechanism(s) underlying this system remains largely undefined. This study aims to examine the influence of induction/inhibition of HO-1 on atherosclerotic plaque using pharmacological approaches and to elucidate potential mechanisms. Rabbits were randomly assigned to receive a standard diet (control group), high fat diet (HFD), HFD plus HO inducer hemin (HFD + H group), and HFD plus an HO inhibitor, zinc protoporphyrin-9 (ZnPP9, HFD + Z group). Atherosclerotic plaque was evaluated using oil red O staining and histological analyses. Immunohistochemistry, western blotting, and RT-PCR were employed to study the expression of HO-1 and endothelin-1 (ET-1). Levels of CO, nitric oxide (NO), eNOS/iNOS activities, NF-κB activity, and TNF-α level were determined. No significant differences of serum lipid levels were observed among the HFD, HFD + Z, and HFD + H groups. In rabbits, HFD induced typical atherosclerotic plaque and increased intima/media thickness ratio, which was markedly reduced in the HFD + H group and further aggravated in the HFD + Z group. Furthermore, hemin increased HO-1 expression, CO levels, and eNOS activity, while decreasing iNOS levels, ET-1 expression, NF-κB activity, and TNF-α level. ZnPP9 caused opposite effects. Induction of the endogenous HO-1/CO system by hemin can prevent atherosclerosis though increasing CO levels, regulating eNOS activity, NF-κB activity, TNF-α levels, and ET-1 levels in rabbits. Our results add new evidence for the importance of HO-1 in the genesis and development of atherosclerosis and provide several possible mechanisms underlying the antiatherosclerosis effects of HO-1.

Abstract 17969: Coronary Plaque Composition in Symptomatic African American and White Patients: Insights From with Coronary CT Angiography

Background: Despite worse cardiovascular outcomes, previous studies have demonstrated that African American (AA) patients have lower coronary calcium score (CCS) compared to Caucasians (CA). The aim of this analysis is to assess the racial differences in coronary plaque burden and composition in symptomatic patients undergoing coronary CT Angiography (CCTA). Methods: A total of 838 symptomatic patients (47% male, mean age: 57±12years) underwent CCS and CCTA for evaluation of chest pain syndrome. Each coronary artery segment was evaluated for the presence of and type (calcified, non-calcified, mixed) of atherosclerotic plaque. Presence and extent of atherosclerotic plaque was compared between AA and CA patients using multivariate regression. Results: African American patients (n=325) were more often males with higher prevalence of diabetes (23% vs. 18%, p=0.044) and hypertension. They less often had any detectable coronary calcifications (46% vs. 55%, p=0.01) as well as lower median CCS score (0 vs. 10, p&lt;0.0001). In univariate analysis, AA patients had a lower prevalence of calcified plaque (34% vs. 42%, p=0.033) with no differences in non-calcified and mixed plaques (Figure). This continued to be significant after adjusting for potential confounders. (OR of AA having more than 2 calcified plaques compared to CA: 0.52, 95%-CI: 0.34 - 0.83, p=0.007). Conclusion: Our analysis suggests that in comparison to Caucasians, symptomatic African-American patients have lower burden of calcified plaque without increase in the presence of non-calcified plaque or mixed plaques as detected by CCTA.