Changes In Atherosclerotic Plaques Research Articles

Ultrastructural changes in atherosclerotic plaques following the instillation of airborne particulate matter into the lungs of rabbits

Epidemiological studies have established that cardiovascular events account for the greatest number of air pollution-related deaths. However, the underlying structural changes are still unknown. To investigate changes in the ultrastructure of atherosclerotic plaques in Watanabe heritable hyperlipidemic (WHHL) rabbits following the instillation of ambient particulate matter air pollution (particles smaller than 10 µm in diameter) into the lungs. WHHL rabbits (n=8) exposed to 5 mg of ambient particles (Environmental Health Centre - 1993 [EHC-93]; suspended in saline and instilled in the airway) twice per week for four weeks were compared with control WHHL rabbits (n=8) treated with saline alone. All abdominal aortic plaques were examined using light and electron microscopy, which showed the following: increased accumulation of macrophage-derived foam cells immediately below the endothelial plaque surface (P=0.04); increased contact between these foam cells and the dense subendothelial extracellular matrix (P<0.005) with reduction (P<0.0001) and fragmentation (P<0.0001) of this matrix; and emigration of macrophage- derived foam cells from the plaques in exposed rabbits. In addition, immunohistochemistry verified the presence of type IV collagen in the thickened extracellular matrix material subtending the endothelium. The ultrastructure of atherosclerotic plaques in EHC-93- instilled rabbits differed from the ultrastructure observed in rabbits that did not receive EHC-93. These ultrastructural differences are consistent with greater endothelial instability in the plaques of atherosclerosis-prone rabbits.

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

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

Abstract 1165: Impact of Gender on Serial Atherosclerotic Changes in Response to Established Medical Therapies

Background: While the importance of coronary artery disease in females has become increasingly recognized, little is known regarding the impact of gender with regard to changes in arterial wall dimensions with progression and regression of atherosclerosis. This study investigated the remodeling response of the artery wall accompanying changes in atheroma burden in response to use of medical therapies, stratified according to gender. Methods: 1533 patients (27.5% female) underwent serial intravascular ultrasound evaluation of a single coronary artery in the context of clinical trials that assess the impact of medical therapies on plaque progression. The relationship between gender and remodeling of the arterial wall at baseline and its serial change in association with plaque progression and regression were studied. Results: Females were older (59 v 57 years, p&lt;0.01), had a higher body mass index (31.5 v 29.5 kg/m 2 , p&lt;0.01), were more likely to have hypertension (86 v 71.5%, p&lt;0.01) and metabolic syndrome (57 v 49%, p&lt;0.01) and less likely to have a history of smoking (57.5 v 73.5%, p=0.01) and myocardial infarction (27.5 v 35.5%, p&lt;0.01). After adjusting for body surface area, females demonstrated a trend towards smaller external elastic membrane (EEM) (226.3 v 234.3 mm 3 , p=0.09) and larger lumen (143.7 v 137.7 mm 3 , p=0.01) volumes. The remodeling index at the most diseased site did not differ between genders (0.95 v 0.95, p=0.95). No differences were observed between genders with regard to changes in EEM (−5.6 v −6.2 mm 3 , p=0.29) and lumen (−4.9 v −4.5 mm 3 , p=0.82) volumes and remodeling index (−0.02 v −0.03, p=0.43) in response to use of medical therapies. Similarly, there were no differences between genders with regard to the percentage of patients undergoing expansion (34.7 v 35.5%, p=0.86) or contraction (20.4 v 21.8%, p=0.69) of lumen volume in association with regression of atherosclerotic plaque. Conclusion: A similar pattern of remodeling of the arterial wall was observed between genders in association with serial changes in atheroscle-rotic plaque. This further highlights our understanding of the pathological interactions between atherosclerosis and the arterial wall in females.

Tracking regression and progression of atherosclerosis in human carotid arteries using high-resolution magnetic resonance imaging

Magnetic resonance imaging (MRI) can accurately and reproducibly measure the volume of atherosclerotic plaque in human carotid arteries. Atherosclerotic plaques may either progress or regress over time, depending on individual risk factors and treatment regimens. This study was designed to determine if regression or progression of human carotid atherosclerosis in patients receiving statin therapy over 24 months can be detected by high-resolution MRI. In 11 subjects who had undergone unilateral carotid endarterectomy and were on statin therapy, volumes for total carotid artery, concentric wall (normal wall), eccentric wall (plaque), and lumen were quantified at 0, 16 and 24 months using a 1.5-T human imager equipped with 6-cm phased array coils. The interobserver mean coefficient of variation (CV) was lowest for the lumen volume (3.1%) and highest for the plaque volume (9.8%). The interscan mean CV was lowest for the total artery volume (3.2%) and highest for the plaque volume (9.9%). As much as 26% regression and 35% progression were observed in individual subject's carotid artery eccentric wall (plaque) volumes over time. Mean eccentric wall volume increased 5% by 16 months and 8% by 24 months. Mean total wall volume increased slightly at both 16 and 24 months (+1.2% and +1.8%). High-resolution MRI provides a noninvasive reproducible method of tracking changes in carotid atherosclerosis. This pilot study detected changes in individual subjects at both 16 and 24 months. MRI tracking of changes in atherosclerotic plaques should prove useful in assessing vascular disease risk and monitoring the efficacy of interventions designed to induce regression or retard progression.

Early benefits of pravastatin to experimentally induced atherosclerosis.

There is little information regarding the time of hypolipidemic treatment of changes in atherosclerotic plaque, tissue cholesterol content, and also for the recovery of endothelial function. To assess the early effects of lipid-lowering treatment on these parameters, six groups of New Zealand male rabbits were studied. Animals in groups I and II were fed regular chow; groups III and IV received a 12-week 0.5% cholesterol diet followed by 12 weeks of 0.05% cholesterol diet. Finally, groups V and VI were fed a 12-week 0.5% cholesterol diet and were then shifted to a regular diet for 12 weeks. During the last four weeks, the rabbits in groups I, III, and V received low-dose pravastatin (2 mg/day), added to the diet. Group IV animals had the highest cholesterol plasma levels (vs. groups I, II, III, and V, p < 0.01) and presented atherosclerotic plaques in a more advanced stage. Nonatherogenic diet was insufficient to restore endothelial function in animals previously fed cholesterol-enriched diets (groups IV and VI). Conversely, pravastatin treatment promoted significant improvement in endothelial function and reduced the progression of atherosclerosis. Marked increase in cholesterol content was seen in aorta and liver in response to the atherogenic diet. However, neither treatment with pravastatin nor nonatherogenic diet was capable of modifying the tissue cholesterol content. Our study supports the hypothesis that the early use of statins can attenuate the progression of atherosclerosis and ameliorate endothelial function. In addition, significant changes in the tissue cholesterol pool probably need a longer period of treatment.

Prevention of cardiovascular disease and the future of cardiovascular disease epidemiology.

Coronary heart disease is preventable. The improved interpretation of risk factors, in vivo non-invasive measuring of arteries, brain and heart, and proven efficacy of both non-pharmacological and pharmaceutical therapies provides the model for both cardiovascular prevention programmes and new epidemiological studies. Risk factors can be subdivided into those related to the development of atherosclerosis with relatively long incubation periods, and risk factors that moderate the changes in atherosclerotic plaque, thrombosis and fibrinolysis, i.e. those with short incubation periods, or proximate risk factors. The level of ApoB containing lipoproteins, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) are the primary determinants of atherosclerosis. Using non-invasive methods of measuring atherosclerosis, we can evaluate the efficacy of intervention to both prevent the development of atherosclerosis and the progression of disease. The importance of proximate risk factors, especially inflammatory markers, is less estimated than long incubation period factors. It is possible that a combination of measures of subclinical atherosclerosis and proximate risk factors may provide the best estimate of the risk of clinical disease, especially among higher risk older individuals. The measurement of subclinical disease and new proximate risk factors (i.e. inflammation, fibrinolysis) may be useful for comparing reported differences in rates of clinical disease among populations and monitoring the emerging epidemic of cardiovascular disease in countries that currently have low death rates due to cardiovascular disease.

Morphologic and Dynamic Changes of Atherosclerotic Plaque at the Carotid Artery Bifurcation: Sequential Imaging by Real-Time B-Mode Ultrasonography

Morphologic and Dynamic Changes of Atherosclerotic Plaque at the Carotid Artery Bifurcation: Sequential Imaging by Real-Time B-Mode Ultrasonography

Morphologic and dynamic changes of atherosclerotic plaque at the carotid artery bifurcation: Sequential imaging by real time B-mode ultrasonography

Occurrence of new symptoms of focal cerebrovascular disease, including completed cerebral infarction, transient cerebral ischemic attack and amaurosis fugax, was correlated with changes in size and morphology of atherosclerotic plaques at the carotid artery bifurcation visualized by real time B-mode ultrasonography. Bilateral serial images of 246 plaques in 123 patients were made in a time interval of 9 to 35 months between initial and follow-up studies. There was a significantly higher incidence of symptoms ipsilateral to plaques that grew [30 (25%) of 121] than of symptoms ipsilateral to plaques that diminished or remained unchanged [8 (8%) of 98] (p less than 0.001). Plaques that became hemodynamically obstructive by causing disruption of laminar flow or reduction of distal perfusion pressure at the ophthalmic artery were associated with a higher frequency of symptoms [12 (40%) of 30] than were nonobstructive plaques [26 (13%) of 201] (p less than 0.001). There was also a strong association between symptoms and plaque configuration. Mural plaques growing in a crescentic configuration along the wall of the carotid bifurcation between the first and second examination had a higher incidence of symptoms [22 (40%) of 56] than did plaques that grew but maintained a nodular configuration [8 (12%) of 65] (p less than 0.001), although the same proportion of each became hemodynamically obstructive. Sequential visualization of atherosclerotic plaques by real time B-mode ultrasonography of the carotid bifurcation may provide a method for studying the pathogenesis of arterial thrombosis.

Platelet-neutrophil interactions in the eicosanoid pathway.

Trauma to blood vessels or degenerative changes in atherosclerotic plaques result in exposure of structures in the subendothelium, such as collagen, which in its native state is stimulatory for platelet adhesion and subsequent activation (Marcus, 1988). Platelet activation is also accompanied by initiation of the blood coagulation cascade, culminating in the formation of thrombin. Collagen and thrombin are capable of stimulating the oxygenation of free arachidonate, thereby activating the eicosanoid pathway in both platelets and endothelial cells. Many of the eicosanoids which form are actually autacoids with significant biological properties.