出版社：American Society for Biochemistry and Molecular Biology
摘要：Cholesteryl ester transfer protein (CETP) inhibitors increasehigh density lipoprotein-cholesterol (HDL-C) in animals andhumans, but whether CETP inhibition will be antiatherogenicis still uncertain. We tested the CETP inhibitor torcetrapibin rabbits fed an atherogenic diet at a dose sufficient to increaseHDL-C by at least 3-fold (207 ± 32 vs. 57 ± 6mg/dl in controls at 16 weeks). CETP activity was inhibitedby 70–80% throughout the study. Non-HDL-C increased inboth groups, but there was no difference apparent by the study'send. At 16 weeks, aortic atherosclerosis was 60% lower in torcetrapib-treatedanimals (16.4 ± 3.4% vs. 39.8 ± 5.4% in controls)and aortic cholesterol content was reduced proportionally. Serafrom a separate group of rabbits administered torcetrapib effluxed48% more cholesterol from Fu5AH cells than did sera from controlanimals, possibly explaining the reduced aortic cholesterolcontent. Regression analyses indicated that lesion area in thetorcetrapib-treated group was strongly correlated with the ratioof total plasma cholesterol to HDL-C but not with changes inother lipid or lipoprotein levels. CETP inhibition with torcetrapibretards atherosclerosis in rabbits, and the reduced lesion areais associated with increased levels of HDL-C.Supplementary key words cholesteryl ester transfer protein • cholesterol efflux • reverse cholesterol transport
Abbreviations: apoB, apolipoprotein B; AUC, area under the curve; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; FC, free cholesterol; FPLC, fast protein liquid chromatography; HDL-C, high density lipoprotein-cholesterol; TPC, total plasma cholesterol
