The effects of dietary cholesterol on atherosclerosis and coronary heart disease (CHD) in rabbits
Date
2001
Authors
Zhang, Bin
Major Professor
Advisor
Ahn, Dong U.
Committee Member
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Abstract
A total of 30 New Zealand White (NZW) rabbits were fed diets containing 0, 1, 2, 4 or 8 g cholesterol per kg for 3 months to determine the dose response of dietary cholesterol on atherosclerosis and lipid metabolism changes in rabbits. Plasma cholesterol concentrations of rabbits increased proportionally with the increase of dietary cholesterol levels during the first 4 weeks and then remained stable until the 12th week. Plasma triacylglycerols and plasma TBARS of rabbits fed 2 g, 4 g or 8 g per kg diet gradually increased with feeding time, but those of rabbits fed 1 g per kg diet were not different from the control. The TBARS of liver tissues increased with dietary cholesterol levels, and liver of rabbits fed 8 g dosage had significantly higher TBARS than other dosages. Cholesterol and lipid content in plasma and RBC membranes increased proportionally with dietary cholesterol. The major changes in fatty acid composition in RBC membranes can be summarized as an increase in PUFA (polyunsaturated fatty acids) and UFA (unsaturated fatty acids) and a decrease in SFA (saturated fatty acids). The percentage of 18:2, 18:1 and 16:1 in RBC membranes increased, but 16:0 and 18:0 decreased. In plasma, PUFA were increased. Aortas from rabbits that received 4 g or 8 g cholesterol per kg diet had massive atherosclerotic lesions. Atherosclerotic plaques were diffuse, with great variability.
Aortas of rabbits that received 0 g or 1 g dosage had only a few small lesions with most of the aorta appearing normal. The hearts and livers of rabbits that received 4 g and 8 g dosages had extensive atherosclerotic changes. This indicated that the hypercholesterolemia-induced atherosclerosis was observed in rabbits only when the levels of dietary cholesterol were high ([Greater than or equal to symbol] 2 g cholesterol/kg diet). As much as 1 g cholesterol/kg diet, which still is considered a very high cholesterol level, produced no pathologic symptoms in NZW rabbits after 3 months of feeding. Therefore, 2 g cholesterol/kg diet is an optimal dosage for lipid-lowering drug research in NZW rabbits, 1 - 2 g cholesterol/kg diet should be considered as optimal dosage for dietary cholesterol oxide study in rabbits. According to present study, there exists a dose response relation between dietary cholesterol, atherosclerosis and CHD. Dietary cholesterol modulates lipid synthesis and fatty acid composition of RBC membrane and plasma in NZW rabbits.
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