Production Of Atherosclerosis Research Articles

Therapeutic response of vascular lesions is better in familial hypercholesterolaemia (fh) than in non-fh subjects

Objectives: The lipid hypothesis was initially based upon Anitchkov's production of atherosclerosis in rabbits by diet-induced hypercholesterolaemia. Cessation of cholesterol feeding reversed the hypercholesterolaemia and reduced the severity of aortic lesions. Marked similarities exist between the location and composition of atheromatous plaques in this animal model and lesions in humans with FH. Retrospective analysis of angiographic trials suggests that cholesterol-lowering by statins and/or apheresis results in regression of coronary lesions in FH but only reduced their progression in non-FH subjects, despite similar percentage decreases in LDL-C.

Of cholesterol-fed rabbits and LDL receptor-deficient men

The lipid hypothesis, born in St Petersburg 100 years ago, was based upon Anitschkow's production of atherosclerosis in rabbits by diet-induced hypercholesterolaemia. Withdrawal of the diet reversed the hypercholesterolaemia and reduced the severity of aortic lesions. Striking similarities exist between the location and composition of atheromatous plaques in this animal model and lesions in humans with familial hypercholesterolaemia (FH). Retrospective analysis of angiographic trials suggests that cholesterol-lowering by statins and/or apheresis results in regression of coronary lesions in FH but only reduces their progression in non-FH subjects, despite similar percentage reductions in LDL cholesterol (C).

Atherosclerosis risk factors: the possible role of homocysteine.

Atherosclerosis is the leading cause of death in North America. It is characterized by thickening of the coronary artery wall by the formation of plaques, resulting in reduced blood flow. Plaque rupture and the consequent thrombosis may lead to sudden blockage of arteries and causing stroke and heart attack. In the last several decades, more than 250 factors associated with the development of coronary artery disease have been identified. Recently, a relationship between atherosclerosis and elevated homocysteine level in the blood has been established. The mechanism for the production of atherosclerosis by homocysteine has been investigated. When human hepatoma cells (HepG2) were incubated with 4 mM homocysteine, enhancements in the production of cholesterol and secretion of apolipoprotein B-100 were observed. The stimulatory effect on cholesterol synthesis was mediated via the enhancement of HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol biosynthesis. Cholesterol appears to play an important role in the regulation of apoB-100 secretion by hepatocytes. It is plausible that the increase in apoB secretion was caused by the elevated cholesterol level induced by homocysteine. The ability of homocysteine to produce a higher amount of cholesterol and promote the secretion of apoB would provide a plausible mechanism for the observed relationship between hyperhomocysteinemia and the development of atherogenesis and coronary artery disease.

Short-term feeding of unsaturated versus saturated fat in the production of atherosclerosis in the rat

Complex diets containing either 40% peanut oil, corn oil, or butter were fed to weanling rats for 3 months. The rats fed the peanut oil-containing diets developed intimal spindle cell lesions similar in many respects to early human atherosclerotic lesions. Rats receiving the butter-containing diets developed foam cell lesions which do not resemble human atherosclerosis. Under electron microscopy the spindle cells were of the smooth muscle type. They appeared more undifferentiated than the smooth muscle cells seen in aortic lesions in rats fed butter-containing diets for 12 months in a previous experiment. The primitive nature of the cells in the present experiment may have been due to their age, their unsaturated fatty acid environment, or other factors. The difference in serum fatty acids was possibly an important factor determining the type of lesion produced, since both the peanut oil- and butter-fed rats had much the same degree of hyperlipemia as shown by similar serum cholesterol and triglyceride levels. Both the peanut oil- and butter-fed rats showed a sharp drop in the relative percentage of serum arachidonic acid, even though the peanut oil-fed group had excessively high levels of serum linoleates. The absolute level of serum arachidonic acid, however, changed very little.

Nutrition in Relation to Arteriosclerosis

Since arteriosclerosis is now regarded as a metabolic disorder, nutrition is considered one of the important factors in its development, treatment and prevention.Experimental production of atherosclerosis has been concomitant with production of high serum cholesterol levels.Saturated fats in the diet increase serum cholesterol, while polyunsaturated fats reduce it. The author believes that the total caloric intake is the most important influence on serum cholesterol.Dietary modifications are suggested which will reduce the caloric intake of fat.

IS THERE A RELATION BETWEEN DIET AND BLOOD CHOLESTEROL?

THE LEVEL of the blood cholesterol varies with certain disease states, and recently some workers have thought that a high level may be related to the development of atheromatosis. It has been suggested by Dock 1 and by others 2 that the amount of cholesterol in the diet is a factor in determining the concentration of this material in the blood and in the production of atheromas. Doubt has been expressed, however, concerning the importance of the dietary cholesterol as a controlling factor of the blood level, and also as to its etiologic significance in atherosclerosis. 3 Many assumptions of those favoring a dietary factor in the production of atherosclerosis have been based on the fact that in certain races whose members ingest less cholesterol and animal fat this change in the arteries is less prominent. Since so many other known and unknown variables may be present, it is obvious