Effects of acyl-CoA: cholesterol O-acyltransferase inhibition on cholesterol absorption and plasma lipoprotein composition in hamsters.
1. The ACAT inhibitors, CL 277082 and SA 58-035 were administered for 7 days to hamsters fed diets containing 0.5% cholesterol. 2. Both agents inhibited cholesterol absorption, decreased hepatic. VLDL and IDL cholesterol esters, plasma HDL and HDL apoE and A-I. 3. In addition, CL 277082 treatment produced significant decreases in plasma cholesterol, VLDL apoB and plasma IDL. 4. The cholesteryl esters in VLDL and LDL but not HDL were more polyunsaturated in CL 277082 treated animals. 5. These results support the hypothesis that ACAT inhibition in the cholesterol fed hamster results in an inhibition of dietary cholesterol absorption, thus limiting the cholesterol supply required for the hepatic production of triglyceride-rich lipoproteins.
Schnitzer-Polokoff
R
R
Cardiovascular Pharmacology, Schering-Plough Research, Bloomfield, NJ 07003.
Compton
D
D
Boykow
G
G
Davis
H
H
Burrier
R
R
D000042:Absorption; D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D002784:Cholesterol / Q000493:pharmacokinetics*; D006224:Cricetinae; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D001053:Apolipoproteins; D008074:Lipoproteins; D002784:Cholesterol; D002785:Sterol O-Acyltransferase