Development Of Experimental Atherosclerosis Research Articles

Effect of lecithin on the development of experimental atherosclerosis in rabbits

Thirty male mongrel rabbits were divided into 3 equal groups: (1) controls, (2) animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, and (3) HFD + lecithin. The experiment lasted 12 weeks. In animals receiving a HFD (group II) the QRS interval (ECG) was significantly prolonged, and the concentration of lipid fractions (except for HDL-cholesterol) and malondialdehyde (MDA) in the blood was markedly elevated. Distinctly lower concentrations of zinc in the serum and cytochrome P-450 in the liver microsomes were observed. When administered together with the HFD, lecithin normalized QRS interval duration, inhibited the diet-induced lipid metabolism disturbances, reduced MDA concentrations and increased zinc concentrations in the serum. Elevated under the influence of lecithin, the content of cytochrome P-450 in the liver microsomes was shown. Surface area of the lipid deposits at 12 weeks, measured planimetrically averaged 24.43% in HFD-fed animals vs 9.28% in lecithin-treated rabbits. We conclude that lecithin is responsible, not only for the hypolipidaemic properties, but also for the antiatherosclerotic action in rabbits.

Randomized, controlled trial of antioxidant vitamins and cardioprotective diet on hyperlipidemia, oxidative stress, and development of experimental atherosclerosis: the diet and antioxidant trial on atherosclerosis (DATA).

The effects of administration of guava and papaya fruit (100 g/day), vegetables, and mustard oil (5 g/day) (group A); antioxidant vitamins C (50 mg/day) and E (30 mg/day), plus betacarotene (10 mg/day) (group B); a high-fat (5-10 g/day) (group C); or a low-fat (4-5 g/day) diet (group D) were compared over 24 diet weeks in a randomized fashion, while all groups of rabbits (five in each of four groups) received a hydrogenated fat diet (5-10 g/day) for a period of 36 weeks. After 12 weeks on the high-fat diet, each group of rabbits had an increase in blood lipoproteins. The fruit and vegetable-enriched prudent diet (group A) caused a significant decline in blood lipids at 24 and 36 weeks, whereas the lipid levels increased significantly in groups C and D. Group A also had a significant rise in vitamin E (2.1 Umol/l), C (10.5 Umol/l), A (0.66 Umol/l), and carotene (0.08 Umol/l) and a decrease in lipid peroxides (0.34 nmol/ml at 36 weeks, whereas the levels were unchanged in groups C and D. Group B rabbits had a significant and greater increase than group A in plasma vitamins E, C, A, and carotene; a rise in HDL cholesterol; and a greater decrease in lipid peroxides after 24 and 36 weeks of treatment. After stimulation of lipid peroxidation in all rabbits, 3 of 5 group C and 2 of 5 group D rabbits died due to coronary thrombosis, whereas in groups A and B there were no deaths, indicating that antioxidant therapy can provide protection against lipid peroxidation and free radical generation. Aortic lipids and sudanophilia, indicating atherosclerosis, were significantly higher in groups C and D than in groups A and B. Fatty streaks and atheromatous and fibrous plaques were noted in all the rabbits in groups C and D. Intimal fibrosis and medial degeneration were also present in the group C rabbits. While group A (36.4 +/- 4.4 microns) and group B (37.1 +/- 4.2 microns) rabbits had minimal coronary artery plaque sizes, group C (75.4 +/- 10.6 microns) and group D rabbits (69.5 +/- 6.2 microns) had significantly greater plaque sizes. Aortic plaque sizes were also greater in groups C and D than in groups A and B. It is possible that combined therapy with antioxidant vitamins C, E, and carotene, and a diet rich in antioxidants, could independently inhibit free radical generation and the development of atherosclerosis.

The effect of population density on the development of experimental atherosclerosis in female mice

The effect of cage population density on plasma lipids and the development of atherosclerosis was examined in female C57BL/6 mice. Mice were housed at a density of one, two or five animals per cage and fed an atherogenic diet for 28 weeks. Subsequently, the animals were bled, sacrificed, the hearts removed and the extent of fatty lesion development in the aorta examined and quantified. As the population density increased, there was a statistically significant increase in total cholesterol levels, VLDL + LDL cholesterol levels, the VLDL + LDL/HDL ratio and lesion severity. These differences are due to the psychosocial stress associated with living within a confined space with high population density over an extended period of time.

Effects of dexamethasone on experimental atherosclerosis in cholesterol-fed rabbits.

We studied the effects of a synthetic adrenocortical steroid, dexamethasone, on the development of experimental atherosclerosis in cholesterol-fed rabbits. Daily intramuscular injection of dexamethasone (0.125 mg/day) remarkably inhibited the aortic atherosclerosis induced by feeding a 1% cholesterol-rich diet for 8 weeks, although it aggravated diet-induced hyperlipidemia. Histologically, less foam cell accumulation was observed in the atherosclerotic lesions of the dexamethasone-treated rabbits as compared with the control animals. When rabbits were fed a normal chow diet for 10 weeks after receiving the 1% cholesterol-rich diet for 8 weeks, no regression of atherosclerotic lesions was observed with the daily injection of dexamethasone (0.125 mg/day); however, the drug again tended to inhibit further progression of atherosclerosis. The anti-atherogenic mechanism of dexamethasone may involve an inhibition of recruitment of blood monocytes and the insudation of atherogenic lipoproteins, mainly beta-very low density lipoprotein (beta-VLDL) in the present experiments, into the aortic intima, or it may involve a change in the size and structure of the lipoproteins, resulting in their decreased passage through the aortic endothelium into the intima.

Effect of selenium and vitamin E on the development of experimental atherosclerosis in rabbits

Male mongrel rabbits, divided into 5 groups (1) controls, (2) animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + selenium, (4) HFD + vitamin E, (5) HFD + selenium + vitamin E, were treated for 12 weeks. In the groups receiving selenium and/or vitamin E, the elevation of serum total lipids, β-lipoproteins total cholesterol and triglyceride was markedly suppressed. HDL cholesterol in these groups of animals was increased. The cytochrome P-450 content in liver microsomes was increased, and the concentration of malondialdehyde in the blood plasma of rabbits was significantly decreased, while thyroid hormones (T 4, T 3), cortisol and insulin level were increased. Surface area of the lipid deposits at 12 weeks measured planimetrically averaged 76% in HFD-fed animals but only 28% in selenium + vitamin E treated rabbits. The important finding of this study is that combination of selenium and vitamin E, results in an intensified effect on the improvement of metabolic processes and on the reduction of atherosclerotic plaque formation.

Effects of ethanol on the development of experimental atherosclerosis and cardionecrosis in rats

The influence of chronic ethanol intoxication upon vitamin D-induced damage of cardiovascular system in rats was examined. Eighty rats, divided into 16 groups according to sex and age, were intoxicated with ethanol as the only source of liquid. Control rats drank water only. After 6 months of ethanol intoxication, part of ethanol and part of water-drinking rats received 3 × 100,000 IU vitamin D/rat, in order to induce atherosclerosis and heart muscle necrosis. The results of the described experiment revealed that the degree of circulatory system damage after chronic ethanol intoxication and vitamin D treatment was dependent on the age of the animals at the beginning of the experiment. Ethanol intoxication intensified vitamin D-dependent heart muscle necrosis in young individuals. In old rats chronic alcohol intoxication diminished atherosclerosis induced by vitamin D.

Effect of pollen extract on the development of experimental atherosclerosis in rabbits

Our previous studies have shown that the pollen extract, Cernitin, reveals lipid-lowering properties in animals and humans. The present study was designed to investigate the influence of Cernitin on the development of experimental atherosclerosis in rabbits over a period of 12 weeks. Forty male mongrel rabbits were divided into 4 equal groups: (1) controls, (2) animals receiving high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + pollen extract, and (4) HFD + clofibrate. The most pronounced reduction in lipid metabolism and in the severity of plaque formation occurred after the pollen extract had been applied. The total cholesterol content in serum and liver homogenate was depressed by 67% and 45%, respectively, while the serum HDL cholesterol and a-lipoproteins level was increased by 19% and from 7.73% to 21.73% respectively. The cytochrome P-450 content in the liver microsomes was elevated by 98% (nmol/g liver). Atherosclerotic plaque intensity at 12 weeks, measured planimetrically, averaged 85.5% in HFD-fed animals vs 33.7% in pollen extract-treated rabbits. These findings suggest that Cernitin, in addition to significantly lowering serum lipid levels in rabbits on an experimental diet, may modify lipid deposition in major arteries.

Biphasic response of intimal prostacyclin production during the development of experimental atherosclerosis

Feeding a cholesterol rich diet (0.3%) to rabbits for up to 10 weeks resulted in morphological changes of the vascular wall. Microscopic evaluation of the aorta revealed a lipid infiltration and an intimal thickening containing foam cells, which both became more pronounced as the cholesterol feeding was more prolonged. The intimal prostacyclin production showed a transient increase after 2 weeks, but was significantly decreased after 6 weeks of diet and remained at this low level during the rest of the experiment. No significant changes in formation of thromboxane B 2 by the platelets could be observed, whereas the production of 12-HETE was enhanced.

Atherogenesis in experimental uremia

The development of experimental atherosclerosis was studied in subtotally nephrectomized rats which were subjected to preimmunisation with horseradish peroxidase and subsequent feeding with atherogenic diet. Both in shamoperated pair-fed control animals and in uremic animals, the atherogenic diet caused hyperlipemia which was more pronounced in uremic than in control animals (control animals: triglycerides 1.11 ± 0.04 mmol/l; cholesterol 5.82 ± 0.21 mmol/l; uremia: triglycerides 1.33 ± 0.06; cholesterol 10.9 ± 0.31). An increase of cholesterol was seen both in the VLDL and in the LDL fractions. Despite more pronounced hyperlipemia, lipid concentration in the aortic wall was not increased nor were more marked histological abnormalities encountered in the aorta of uremic animals (cholesterol-fed control: cholesterol 95.4 ± 4.4 μg/mg protein; phospholipids 2.42 ± 0.9 μ/ml protein; cholesterol-fed uremia: cholesterol 96.8 ± 4.9; phospholipids 2.52 ± 0.8). The results suggest that despite hyperlipemia short-term experimental renal insufficiency does not promote atherogenesis.

動脈硬化症の発生進展過程における血液線溶活性の意義

A total of 29 young female arbino rabbits weighing around 2kg each were used in 2 experimental studies.Ex. 1: In 9 rabbits, the determination of dose and method of UK administration, which enoughly provoked of blood fibrinolysis, initially examined.Ex. 2: In order to evaluate the significance of the accerelated blood fibrinolysis on the pathogenesis and the development of atherosclerosis, 20 rabbits were divided into 2 subgroups (UK group, Control group). The UK group was administered UK via marginal ear vein 2 times every day during only initial 2 weeks and simultaneously fed a lanolin diet contained 1.4% cholesterol throughout experimental period. The control group was fed a lanoline diet alone in the same period.We concluded followings.Ex. 1: When 30, 000 IU/kg/day of UK was initially administered during first one week and then grdually decreased bolus of UK next week, it could be enoughly accerelated blood fibrinolysis.Ex. 2: (1) In both groups, TC remarkably increased at 1 and 4 weeks. No significant difference between both groups was observed throughout the experiment.(2) Although no remarkable changes of fibrinogen contents were recognized in UK group throughout experimental period, in control group it remarkably increased at 4 weeks and after that gradually increased up to 10 weeks. However, there was significant difference between both groups at 2 weeks.(3) In control group, ELT grdually prolonged up to 2 weeks.In contrast to it significantly shortened at 1 and 2 weeks in UK group.(4) In UK group, a lysis area was inclined to increase up to 2 weeks, and after 6 weeks slightly weakened lysis area were recognized.(5) FDP significantly incerased at 2 weeks in control group, but significantly increased at 1 and 8 weeks in UK group.(6) A proportion of atheromatous lesion of thoracic aorta was less recognized in UK group than that in control group.(7) The stratification of foam cells in the intima of aortic arch were prominently observed in control group than in UK group. And the proliferation of intimal smooth muscle cells were remarkably recognized in UK group than in control group.Above the results lead us to believe that the accerelated blood fibrinolysis due to administration of UK during the initial 2 weeks of experimental period would be one of the important retarding factors of the generation and the development of experimental atherosclerosis in rabbits.

Influence of chronic carbon disulphide intoxication on the development of experimental atherosclerosis in rats.

Rats fed on atherogenic diets containing 2% cholesterol and 0.5% cholic acid with or without 0.15% thiouracil were exposed to carbon disulphide (CS2) vapours (1 mg/l of air), five hours a day, six days a week for 6-10 months. Serum and aorta lipid contents were determined, and the extent of atherosclerotic changes was investigated. The following effects of chronic exposure to CS2 were found: (1) slower gain in body weight when rats were fed on atherogenic diet; (2) greater increase in serum cholesterol content (after thiouracil supplemented diet); (3) moderate increase in total cholesterol content in the aorta wall with a significantly increased esterified cholesterol fraction but none in phospholipid level in this tissue; and (4) more advanced lipid infiltrates of coronary arteries and endocardium, the latter predominantly in the aortic valves. These results together with data from previous studies indicate that metabolism of arterial lipids participates in the process of artheroma formation after chronic exposure to CS2 vapours.

Effect of hydrocortisone on the development of experimental atherosclerosis in rabbits

The role of the immunocompetent system in the development of experimental atherosclerosis was studied in experiments with 51 rabbits given hydrocortisone injections. Hydrocortisone produced atrophy of T and B systems of the lymph nodes and spleen. Under these conditions the experimental sclerosis developed little regardless high lipid blood level. This circumstance provides one more argument of the role played by the immunologic factors in the formation and development of atherosclerosis.

Effect of immunization with small doses of antigen on the development of experimental atherosclerosis

Immunization of rabbits suffering from experimental hyperlipemia with human gamma-globulin (a total dose of 150 mg) or with disintegrated yeast Candida albicans (a total dose of 62 mg) inhibited the development of hyperlipemia and atherosclerosis. The effect was more pronounced in animals immunized on the 6th experimental week than in those immunized on the 9th week.

Progression and regression of experimental athrosclerotic lesions.

The prerequisite for development of experimental atherosclerosis in the rabbit and all other experimental models is hyperlipemia. Hyperlipemia can be induced in the rabbit by adding cholesterol to the diet or using a diet with a high content of saturated fat. Lipid infiltration into the wall of the proximal aorta begins within hours following the increase in blood cholesterol1. The earliest lesion morphologically is granular appearing stainable lipid in the interstitial tissue often associated with elastic fibers. Continued hypercholesterolemia eventuates in a foam cellular infiltrate in the intima and inner media associated with proliferation of smooth muscle cells and appearance of a band of smooth muscle cells beneath the endothelial lining1,2. Necrotic cells are found in the lesion usually near the media2. The lipid content of this lesion like that of all other experimental models and man is mostly cholesterol as cholesteryl esters3. The cholesterol in the lesions is derived from the blood4.

Effect of ethyrazole and parmidine on the development of experimental atherosclerosis in rabbits

In rabbits receiving cholesterol with the diet for 3–4 months the accumulation of total cholesterol in the aorta and the degree of severity of atherosclerosis of the aorta were reduced by administration of ethyrazole and parmidine. These substances had no substantial effect on the blood cholesterol, triglyceride, and phospholipid levels of these animals.

Effect of injury to hypothalamic nuclei on morphological and functional state of the hypothalamic-pituitary system and the development of experimental atherosclerosis

Injury to individual nuclei of the anterior and middle parts of the hypothalamus in rabbits by electrocoagulation (anode, 5 mA, 20–25 sec) through previously implanted electrodes was followed by changes in the morphological and functional state of the hypothalamic-pituitary neurosecretory system (HPNS). The closer the focus of injury to the region of the supraoptic nuclei, the higher the functional activity of HPNS. If injury to individual hypothalamic nuclei was combined with administration of an atherogenic diet, marked morphological and functional changes were detected both in HPNS and in the adrenals, but in animals with experimental atherosclerosis, this disease assumed a more severe form under these conditions than in animals simply receiving the atherogenic diet. The results of these experiments point to a close connection between the genesis of atherosclerosis and neurogenic factors.

Effect of functional strain of the CNS and endocrine disturbances on development of experimental atherosclerosis in dogs

Functional strain on the CNS was combined in chronic experiments on seven dogs with other factors changing the hormonal status of the animal-castration and injection of mercazolyl in doses of 1.5–2.5 mg/kg (group 1). The six control dogs (group 2) underwent castration and injection of mercazolyl only. The animals of group 1 developed persistent hypercholesteremia, atherosclerotic changes in various intramural arteries, especially of the myocardium, and also degenerative changes in the parenchyma of certain organs, which were not found in the animals of group 2. The results of this investigation demonstrate the important role of functional strain on the CNS as a leading “risk” factor responsible for disturbances of the regulation of lipid metabolism and the development of atherosclerotic changes in the vessels.

Effect of diosponin on the hypothalamic neurosecretory system and the development of experimental atherosclerosis

Effect of diosponin on the hypothalamic neurosecretory system and the development of experimental atherosclerosis

Effect of n-alkanes on development of experimental atherosclerosis in rabbits

Effect of n-alkanes on development of experimental atherosclerosis in rabbits

Effect of cyclophosphamide on the development of experimental atherosclerosis in rabbits

Effect of cyclophosphamide on the development of experimental atherosclerosis in rabbits