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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:203-210.)
© 1997 American Heart Association, Inc.

Articles

Plasma Kinetics of Cholesteryl Ester Transfer Protein in the Rabbit

Effects of Dietary Cholesterol

Ruth McPherson; Paulina Lau; Paul Kussie; Hugh Barrett; Alan R. Tall

the Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, Ottawa, Canada (R.M., P.L.); Resource Facility for Kinetic Analysis, Center for Bioengineering, University of Washington, Seattle (H.B.); and the Division of Molecular Medicine, Columbia University College of Physicians and Surgeons, New York, NY (P.K., A.R.T.).

Correspondence to Dr Ruth McPherson, Room H441, 1053 Carling Ave, Ottawa, Canada K1Y 4E9. E-mail rmcphers@heartinst.on.ca.

The plasma kinetics of recombinant human cholesteryl ester transfer protein (rCETP) were studied in six rabbits before and after cholesterol feeding (0.5% wt/wt). The rCETP, labeled with the use of the Bolton Hunter reagent, was shown to retain neutral lipid transfer activity. After intravenous infusion, labeled rCETP associated with rabbit lipoproteins to an extent similar to endogenous rabbit CETP (62% to 64% HDL associated). The plasma kinetics of CETP, modeled with the use of SAAM-II, conformed to a two-pool model, likely representing free and loosely HDL-associated CETP (fast pool) and a tightly apo (apolipoprotein) AI–associated (slow pool) CETP. The plasma residency time (chow diet) of the fast pool averaged 7.1 hours and of the slow pool, 76.3 hours. The production rate (PR) into and the fractional catabolic rate (FCR) of the fast pool were 20 and 10 times the PR and FCR, respectively, of the slow pool. In response to cholesterol feeding, CETP PR, FCR, and plasma mass increased by 416%, 60%, and 230%, respectively. There was a strong correlation (r=.95, P=.003) between the increase in rabbit plasma CETP and the modeled increase in CETP PR in response to cholesterol feeding, suggesting that labeled human rCETP is a satisfactory tracer for rabbit plasma CETP. CETP is catabolized by distinct pools, likely corresponding to an apo AI–associated (slow) pool and a free and/or loosely HDL-associated (fast) pool. Factors that alter the affinity of CETP for HDL would be predicted to result in altered CETP catabolism. The effect of dietary cholesterol on plasma CETP mass can be explained largely by the effects on CETP synthesis, consistent with the observed effects of cholesterol on tissue mRNA levels.

Key Words: CETP • lipid transfer protein • HDL • dietary cholesterol • lipoprotein kinetics

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