CHOLESTERYL ESTER TRANSFER PROTEIN-INHIBITION IN HYPERCHOLESTEROLEMICHAMSTERS - KINETICS OF APOPROTEIN CHANGES

Inhibition of cholesteryl ester transfer protein (CETP) activity in hy percholesterolemic hamsters results in elevated high-density lipoprote in (HDL) cholesterol, an increase in HDL size, and the appearance of a polipoprotein E (ape E)-rich, apo A-I-poor particles. The present stud y has focused on the kinetics of apoprotein redistribution among the H DL particles and the relative increase in HDL-associated apo E and CET P in hypercholesterolemic hamsters, following inhibition of transfer a ctivity using the monoclonal antibody, TP2. A 60% inhibition in CETP a ctivity 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 f raction throughout the duration of the study. In contrast, while CETP was also detected on large HDL particles, this distribution shifted ba ck toward the pretreatment pattern by 14 d. The dynamic changes in apo protein distribution may represent a compensatory physiologic response following disruption of reverse cholesterol transport.