Cholesteryl ester transfer protein inhibition in hypercholesterolemic hamsters: kinetics of apoprotein changes

Inhibition of cholesteryl ester transfer protein (CETP) activity in hypercholesterolemic hamsters results in elevated high-density lipoprotein (HDL) cholesterol, an increase in HDL size, and the appearance of apolipoprotein E (apo E)-rich, apo A-I-poor particles. The present study has focused on the kinetics of apoprotein redistribution among the HDL particles and the relative increase in HDL-associated apo E and CETP in hypercholesterolemic hamsters, following inhibition of transfer activity using the monoclonal antibody, TP2. A 60% inhibition in CETP activity was observed 24 h after antibody injection and was associated with an increase in HDL cholesterol and HDL size. Increased amounts of apo E were associated with these HDL particles and remained in this fraction throughout the duration of the study. In contrast, while CETP was also detected on large HDL particles, this distribution shifted back toward the pretreatment pattern by 14 d. The dynamic changes in apoprotein distribution may represent a compensatory physiologic response following disruption of reverse cholesterol transport.