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Query: UMLS:C0004153 (atherosclerosis)
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A quantitative study of the size and location of early sudanophilic lesions has been carried out on the aortae of five rabbits. The atherosclerotic lesions were induced by feeding an average of 114 (+/- 3.7) egg yolks over an average period of 83 (+/- 1.7) days. The aortic lesions were visualuized by gross staining with Sudan III and measured by the polar coordinate method. The lesions were almost entirely around orifices: their size was directly proportional to the area of the associated ostium (P less than 0.005). The sudanophilic deposits were located downstream from the ostia in areas believed to experience high shear stresses. The area of the intercostal ostia increased as one proceeded down the thoracic aorta (P less than 0.005). A deviation from the distal distribution pattern was observed where local flow and shear stresses were disturbed. The coronary lesions completely surrounded the ostia, the coeliac lesions had significant proximal components and the left renal and inferior mesenteric lesions were skewed to the right. The study suggests that hemodynamic forces and particularly high shear stress is of considerable importance in both the initiation and localization of early atherosclerotic lesions.
Atherosclerosis
PMID:A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta. 5 82

Polar coordinate mapping was used to determine the rate of growth of individual sudanophilic lesions on the aortic wall around several major branches of the aortae of cholesterol fed rabbits. Four groups, with 6 8-month old male albino white rabbits in each, were used in the study. One group served as a control and the remaining 3 were fed a diet of 2% cholesterol and 6% heated corn oil mixed with ground rabbit pellets for 4, 8, and 10 weeks each. Animals were sacrificed, the aortae removed, stained with Sudan III, pinned at in vivo dimensions, and mapped by the polar coordinate method. No sudanophilic lesions were observed in the control animals. In the experimental groups, the early lesions, except the coronaries, were almost entirely distal to the orifices, and maintained roughly the same contour while spreading around the orifice. The coronary lesions completely encircled the orifices as described previously. As lesions progressed, they became elevated and often granular, so that the lesions themselves may have affected flow profiles around the orifices. Lesions around adjacent orifices were fused in 48% of the cases after 10 weeks on the diet, as opposed to 2% after 4 weeks on the diet. More prolonged experiments were not possible with this diet as the animals developed jaundice and diarrhea. Hemodynamically, these results suggest that early sudanophilic lesions in cholesterol-fed rabbits develop on the aortic wall in areas of high shear stress.
Atherosclerosis 1976 Oct
PMID:The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta. 6 80

The foam cell is viewed as a specific component of the atherosclerotic plaque found in human or experimentally induced in the animal. A study using light microscopy (staining with Sudan III) and electron microscopy was performed on cell cultures derived from rat aortic media. Sudanophilic and electron transparent vacuoles were observed in vitro in 11 week cultures. The sudanophilic cells were either scattered or crowded in clusters; some of them were found in a mitotic phase. Different serums were applied to the cultures starting from the 6th week: either calf serum (continuing the previous treatment), or normocholesterolemic rat serum (NCRS) or hypercholesterolemic rat serum (HCRS). Sudanophilic cells were observed more frequently in the cultures on exposure to HCRS than to NCRS (p less than 0.05). Thus it was possible to induce the formation of foam cells in vitro in cultures of arterial tissue derived from the rat, which is known to be resistant to atherosclerosis.
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PMID:[Formation of xanthomatous cells in vitro from the aortic media of the rat]. 6 56

Eighteen New Zealand white rabbits were placed on a diet containing 0.25% cholesterol and 6% corn oil for periods of up to 6 months. The animals were divided into 4 gours and sacrificed after 2, 3, 4, and 6 months. The aortae were removed, stained with Sudan III, and analyzed with the polar coordinate technique. While the periorificial lesions developed more slowly on this diet than on the diet with 2% cholesterol and 6% corn oil we had used previously, there was no differences in either the location or the shape of the lesions. In the descending thoracic aorta, lesions developed initially distal to orifices; however, significant lateral and proximal components were observed as atherogenesis progressed. The coronary lesions completely surrounded the ostia in all stages of development. The total area of the lesions was more related to time (r = 0.74, P less than 0.01), than to serum cholesterol (r - 0.51, P less than 0.05) or to cholesterol-time product (r = 0.69, P less than 0.01).
Atherosclerosis 1978 Feb
PMID:A quantitative study of the development of sudanophilic lesions in the aorta of rabbits fed a low-cholesterol diet for up to six months. 64 53

The objective of this experiment was to determine the effects of supplemental dietary cholesterol and treadmill exercise on blood plasma cholesterol and development of atherosclerosis in young goats. Eighteen two-week-old goats, assigned to four groups for 22 weeks, were fed 100 g whole milk and, after 14 weeks, 50 g corn and cob meal daily/kg body weight. The four groups received, respectively, 250, 175, 100 and 25 mg cholesterol/kg body weight daily in the milk. From week 10 to week 22 of the experiment half of the goats in each group were exercised on a motorized treadmill at a rate of 6.4 km/h for 15 min daily, five days per week. Addition of cholesterol to the diet increased the mean plasma cholesterol in each of the four groups, but between-group comparisons were statistically significant for only the 250-mg group versus the 25-mg group. Exercise had no effect on plasma cholesterol. Analysis of serial blood samples of 16 of the goats during one day of the experiment indicated no significant diurnal variations. Six males, three exercised and three nonexercised, were sacrificed; all had extensive aortic sudanophilia. Histological preparations from sudanophilic areas of all aortas showed areas of intimal thickening composed of foam cells. These same areas stained strongly for lipid with Oil Red 0. No histological evidence of calcium deposition or fibrous plaques was found.
Atherosclerosis 1977 May
PMID:The effects of supplemental dietary cholesterol and exercise on blood cholesterol and atherosclerosis in the goat. 85 15

Smooth muscle cells from the tunica media of piglet aortae grown under hypoxic conditions undergo the following changes: First, they become modified by partial loss of myofilaments and proliferation of organelles, which are characteristics of young primitive cells. Second, an increase in number of pinocytotic vesicles at and below the cell surface, indicating increased extracellular uptake of material, can be detected. This is followed by accumulation of Oil Red O positive intracytoplasmic granules and vacuoles as well as the subsequent formation of mount-like protrusions. The latter consist of a core of extracellular material and necrotic debris covered with a cap of viable cells. A third feature of the cells subjected to hypoxia is a conspicuous rise in the number of lysosomes. This is considered to be a manifestation of a defense mechanism of the cells to remove undesirable material from cytoplasm. Cells exposed to an atmosphere rich in carbon monoxide exhibit basically the same alterations as those grown under hypoxic conditions; however, formation of mound-like aggregates is less prominent, while the rise in the number of lysosomes is more evident than in the hypoxic cells. The above alterations are similar to changes observed in smooth muscle cells of rabbit with experimental atherosclerosis. It is suggested that whereever the arterial smooth muscle cell is subjected to adverse conditions basically the same mechanism, consisting of dedifferentiation, increased permeability and lysosomal defense reaction, takes place.
Atherosclerosis 1976 Oct
PMID:Light- and electron-microscopic characteristics of artrial smooth muscle cell cultures subjected to hypoxia or carbon monoxide. 98 93

A study was made on the effect of simvastatin (the generic name of MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on coronary atherosclerosis in cholesterol-fed rabbits with focus on the serum lipids and morphology. Twenty-seven Japanese white rabbits were divided according to dosage of simvastatin into four groups as follows, group P (placebo, 5 rabbits), group MK 1 (simvastatin 1mg/kg, 5 rabbits), group MK 3 (simvastatin 3mg/kg, 6 rabbits) and group MK 5 (simvastatin 5mg/kg, 5 rabbits). They were placed on a 0.5% cholesterol atherogenic diet for 16 weeks and measurements were made of the concentration of serum lipids weekly. After sacrifice, the degree of surface involvement (SI) of aorta stained with Sudan III and the degree of coronary stenosis (CS) of the left circumflex artery were measured using an image-processing system. Serum total cholesterol (TC) level and beta-lipoprotein level decreased dose-dependently in MK groups compared with group P. High density lipoprotein cholesterol level increased in groups MK 3 and MK 5 slightly. Triglyceride level decreased in groups MK 3 and MK 5. The progressions of SI and CS were suppressed in MK groups dose-dependently. Integrated TC, that is, sum of the serum TC values obtained at each week multiplied by 7 corresponded more closely to CS than SI. Intimal thickening constructed from large foam cells originated from macrophages and proliferating smooth muscle cells included lipid droplets in MK groups was almost similar in group P. But it was likely that lipid droplets in each smooth muscle cell in MK groups were less than in group P. In conclusion, the development of coronary atherosclerosis in cholesterol-fed rabbits was suppressed dose-dependently by simvastatin and it was suggested that this preventive effect was due to reducing the integrated TC and local action to vessel walls by simvastatin. (Fukuoka Acta Med.)
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PMID:[Preventive effect of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis in cholesterol-fed rabbits]. 202 60

The distribution and progression of coronary arterial and aortic lesions were examined in 40 conventional Watanabe heritable hyperlipidemic (WHHL) rabbits. They were classified according to age into stage I (3-5 months old, 14 rabbits), stage II (6-12 months old; 12 rabbits) and stage III (14-28 months old; 14 rabbits). Fifteen normal Japanese rabbits served as controls. The findings obtained from serial and transverse sections of each of the extramural coronary arteries (ECA) and transverse sections of 4 to 5 equal pieces of whole ventricle for intramural coronary arteries (ICA) were quantified by an image analyzer. Atherosclerosis with positive Sudan III stain was seen in aorta, ECA and ICA over 200 mu in diameter. Atherosclerotic lesions were noted in the aortic arch in stage I rabbits and in the whole aorta in stages II and III rabbits. In ECA, stenosis due to atherosclerosis was noted in 14, 33 and 93% of stages I, II and III rabbits, respectively. Stenosis of over 75% in the orifices of the left and right coronary arteries was noted frequently (71%), while mural thrombi, hemorrhage, intimal rupture and recanalization were seen rarely. Striking features were non-atherosclerotic stenosis with negative Sudan III, seen in the ICA less than 200 mu in diameter of almost all the hearts of stages II and III rabbits. Acute and old myocardial infarction appeared in 5 of the 14 hearts of the stage III rabbits and the infarct-related ECA showed severe stenosis of over 90%. In conclusion, to detect coronary atherosclerosis, serial and transverse sections of ECA are needed. In conventional WHHL rabbits, the incidence of stenosis in ECA is very high, compared with that of the previous reports, and myocardial infarction is due to severe stenosis in ECA. Non-atherosclerotic lesions in ICA occur before the appearance of the atherosclerotic lesions in ECA.
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PMID:Distribution and progression of coronary arterial and aortic lesions in the conventional Watanabe heritable hyperlipidemic rabbit--quantitative analysis. 338 15

Male hamsters were fed a hyperlipidemic diet consisting of standard chow supplemented with 3% cholesterol and 15% commercial butter for 12 months. In about 3 weeks serum total cholesterol doubled, raised 4-fold after the 4th week and after 10 months attained a 17-fold value. Low density lipoproteins (LDL)-cholesterol increased 4-fold after 4 weeks and about 13-fold after 10 months compared to control animals. In the first 2 weeks mononuclear cells began to adhere to the endothelium and a very intense stromal reaction appeared in the intima of the aortic arch. At the end of the 4th week of diet, Oil Red O stainable deposits were visible on the thoracic aorta, mostly on the arch, some of them as isolated, lipid-laden cells and others distributed on focal areas. Smooth muscle cells (SMC) appeared also in the intima of hyperlipidemic hamsters, compared to normal animals which had no macrophages or smooth muscle cells in the intima of the aortic specimens examined. Up to 6 months, smooth muscle cells in the intima and media began to load with lipids, as well as endothelial cells. After 10 months the affected zones looked like human atherosclerotic plaque with huge cholesterol crystal deposits, calcium deposits and necrosis. The endothelium, though very thinned and loaded with lipids, was morphologically intact.
Atherosclerosis 1987 Nov
PMID:The hyperlipidemic hamster as a model of experimental atherosclerosis. 368 79

Both the reproducibility of the surface measurements of aortic atherosclerosis and the agreement between gross inspective and histologic changes were evaluated. Aortas from male broad breasted white turkeys were chosen because of the high incidence of spontaneous and typical atherosclerotic lesions in this animal strain. Ten male turkeys were killed at 33 weeks of age. The aortas were removed including the iliac bifurcation and stained with Sudan III. Each aorta was processed blindly by four pathologists and a computerized planimeter to determine normal areas, sudanophilic areas and areas covered by plaques. The analysis of variance showed significant differences among the four pathologists' measurements of sudanophilic areas (P less than 0.01) and areas covered by plaques (P less than 0.001). The coefficients of variation among the four determinations made by one pathologist on the same aorta were 3.6% for total aortic area; 10.08% for sudanophilic area; 47.6% for the area covered by plaques. On each aorta histology was performed at the level where all the four pathologists recorded the same findings at inspection, namely a normal area, a sudanophilic area, and an area covered by plaques. Important discrepancies occurred between findings at inspection and those of histologic examination: the ten areas classified as "normal" by all the four pathologists at inspection were shown at histologic examination to be normal in only two cases. In one case a musculo-elastic layer and in seven cases a fibro-elastic layer were found. The ten areas classified as "sudanophilic" by all the observers showed a fibro-elastic layer in five cases, a musculo-elastic layer in two cases and normal findings in three cases. The ten areas classified as "covered by plaques" displayed a typical atherosclerotic plaque in all cases but one. In conclusion, our data indicate that the reproducibility of gross inspective methods is low. Important discrepancies exist between findings at inspection and histologic examinations. The relevance of these findings remains to be established as far as the assessment of human atherosclerosis is concerned.
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PMID:The surface measurement of aortic atherosclerosis: critical survey and comparison with histologic findings. 403 Jan 43


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