Key result
Prolonged cholesterol diet lowers total cholesterol ~16% but increases atherosclerotic lesion volume in mice.
Why the study?
The relationship between the duration of a cholesterol diet and the development of atherosclerosis in homozygous apolipoprotein E-deficient mice was evaluated.
Does a longer duration of a cholesterol diet increase the development of atherosclerosis in homozygous apolipoprotein E-deficient mice?
Does a longer duration of a cholesterol diet increase the development of atherosclerosis in homozygous apolipoprotein E-deficient mice?
Absolute Event Rate: 26.75% vs 31.69%
p-value: p=<0.05
A longer duration of a cholesterol diet paradoxically lowers serum cholesterol while accelerating atherosclerotic lesion development in apo E KO mice, likely due to increased cholesterol penetration into the vessel wall and biliary excretion.
Homozygous apolipoprotein E-deficient (apo E KO) mice represent a suitable model for the experimental study of atherosclerosis.The aim of our study was to evaluate the relationship between the duration of a cholesterol diet and the development of atherosclerosis.Apo E KO mice were divided into two groups.Group 1 (n = 8) received a cholesterol diet from the first day of life after birth (through the breast milk of the mothers on a cholesterol diet), Group 2 (n = 6) received a control diet (as well as their mothers) for the first 3 months, and a cholesterol diet from the third month of life.The animals were euthanased by decapitation at the age of five months.Blood was used for the measurement of cholesterol concentrations.From a series of 72 histological sections through the descendent thoracic aorta, 8 samples were selected in a uniform systematic random manner and used for a stereological quantification of atherosclerotic lesions.In comparison with the mice on a cholesterol diet for 2 months (Group 2), the total cholesterol concentration in the mice on a cholesterol diet for 5 months (Group 1) was lower (31.69 ± 4.10 mmol/l and 26.75 ± 3.23 mmol/l, respectively, p< 0.05), and the volume of atherosclerotic lesions was higher (p < 0.04).Although atherosclerotic changes were found in both Groups 1 and 2, we found the atherosclerotic lesions to be significantly more developed in the experimental group fed a cholesterol diet for five months (Group 1) than in the group fed the same diet for two months only (Group 2).It can be concluded that the lower cholesterolemia found in apo E KO mice after five months of a cholesterol diet (Group 1) compared to the group fed the diet for two months only (Group 2), together with accelerated atherosclerosis is probably due to the combination of an increased excretion of cholesterol from the body via production of bile acids, and increased penetration of cholesterol to the vessel wall. Animal model, histology, cholesterol concentration, morphometric analysis, stereology
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Bobková et al. (2005) studied Atherosclerosis (n=14). Cholesterol diet for 5 months vs. Control diet for 3 months followed by a cholesterol diet for 2 months was evaluated on Total cholesterol concentration (p=<0.05). A 5-month cholesterol diet in apo E KO mice led to lower total cholesterol (26.75 vs 31.69 mmol/l; p<0.05) but a higher volume of atherosclerotic lesions (p<0.04) compared to a 2-month diet.