Distribution of 25-hydroxycholesterol in plasma lipoproteins and its role in atherogenesis. A study in squirrel monkeys.
Oxidation products of cholesterol have been shown to be potent inhibitors of cholesterol biosynthesis and also highly toxic to cultured aortic smooth muscle cells. In rabbit experiments, these compounds produced arterial injury resulting in arteriosclerosis. Purified cholesterol only minimally inhibited cholesterol biosynthesis and had no effect on cultured aortic smooth muscle cells. This raises the possibility that plasma lipoproteins containing beta-apoprotein (i.e. LDL and VLDL), which are considered to be atherogenic, may carry more oxidation products than HDL which is not atherogenic [3H]25-hydroxycholesterol and [14C]cholesterol were given only orally to 10 squirrel monkeys (Saimiri sciureus) and blood samples were collected via femoral puncture 24 h after administration. Lipoproteins were separated by ultracentrifugation and the radioactivity in each fraction was counted. Results show that the distribution of labeled cholesterol in VLDL, LDL, and HDL was almost identical to that of unlabeled cholesterol. Most of the radio-activity of 25-hydroxycholesterol was located in LDL & VLDL (55.1% and 34.7%, respectively), only 10.2% was present in HDL. If the radioactivity of 25-hydroxycholesterol were calculated on the basis of the apoprotein content of the lipoprotein micelle, the relative capacity of VLDL and LDL to carry 25-hydroxycholesterol was even greater and more significant than that of HDL (90 X and 42 X, respectively).
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005260:Female; D006888:Hydroxycholesterols / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction; D012453:Saimiri
D002791:Cholesterol, Dietary; D006888:Hydroxycholesterols; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; C007997:25-hydroxycholesterol