Effect of clinofibrate on lipid metabolism of aorta in atherosclerotic rats.
Atherosclerotic lesions formed in the aorta of rats given diet containing propylthiouracil (PTU), vitamin D2 and high cholesterol diet (atherogenic) for 8 weeks. The effect of clinofibrate, which lowers the plasma lipid level, on lipid metabolism in the arterial wall of the atherosclerotic rats was studied. Clinofibrate significantly decreased the high plasma cholesterol level of atherosclerotic rats, which was 823 +/- 256 (mean +/- SD) mg/dl, or about ten times that of control rats (85 +/- 11 mg/dl). On treatment with clinofibrate, the cholesterol level was reduced most in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post heparin plasma, and VLDL-triolein hydrolizing activity in adipose tissue stromal vessels were higher in clinofibrate-treated rats than in atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity was decreased in atherosclerotic rats, and clinofibrate treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity was higher in atherosclerotic rats than in control rats and was lower in clinofibrate-treated rats than in atherosclerotic rats. From these results, it is concluded that clinofibrate modifies enzyme activities in such a way as to cause a reduction of cholesterol accumulation in the arterial wall and lowers the plasma VLDL and LDL cholesterol levels.
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D006016:Glycolates / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D010642:Phenoxyacetates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002788:Cholesterol Esters; D006016:Glycolates; D000960:Hypolipidemic Agents; D010642:Phenoxyacetates; C006231:clinofibrate; D008071:Lipoprotein Lipase