Clofibrate (CPIB) と動脈壁, 血中 Cholesterol

Abstract

Clofibrate (ethyl α-p-chlorophenoxyisobutyrate) has been known to reduce the level of serum cholesterol and triglycerides in rat, dog, monkey and man. In the case of rabbit, however, the lipid lowering activity in serum are uncertain, and its effect on the fatty acid composition in the serum and arterial esterified cholesterol has been less explored. We have examined the effect of clofibrate on cholesterol accumulation in the aorta of rabbits.In the present study, clofibrate caused a reduction of cholesterol and an increase in the ratio of linoleic to oleic acid of cholesteryl ester in the aorta. In the serum, there was no significant difference in cholesterol level between experimental and control groups. Concerning the composition of esterified fatty acids, however, a decrease in the proportion of oleate and an increase in the proportion of linoleate were observed. Reduction in accumulation of aortic cholesterol might be interpreted as follow from these results. It might be possible that a relatively high proportion of polyunsaturated fatty acids in the cholesteryl ester was induced in serum lipoprotein after Clofibrate treatment. Smith and Slater reported that lipids in aortic plaques might be derived from lipoprotein in serum. Consequently, an increase in the ratio of linoleic to oleic acid in artevial wall was derived from serum lipoprotein. Polyunsaturated fatty acid of cholesteyl ester could be hydrolyzed predominantly due to the specificity of cholesteryl ester hydrolase. Cholesteryl ester accumulated in the aortic wall after clofibrate treatment therefore, might be easily eliminated by the enzyme.It seems to be likely that clofibrate might modify the composition of fatty acids of cholesteryl ester in serum and arterial wall, subsequently the relative decrease of aortic cholesteryl ester might be observed.