Apolipoprotein CI is a physiological regulator of cholesteryl ester transfer protein activity in human plasma but not in rabbit plasma

Plasma cholesteryl ester transfer protein (CETP) activity is high in rabbits, intermediate in humans, and nondetectable in rodents. Human apolipoprotein CI (apoCI) was found to be a potent inhibitor of CETP. The aim of this study was to compare the ability of rabbit and human apoCI to modulate the interaction of CETP with HDLs and to evaluate to which extent apoCI contributes to plasma cholesteryl ester transfer rate in normolipidemic humans and rabbits. Rabbit apoCI gene was cloned and sequenced, rabbit and human apoCI were purified to homogeneity, and their ability to modify the surface charge properties and the CETP inhibitory potential of HDL were compared. It is demonstrated that unlike human apoCI, rabbit apoCI does not modulate cholesteryl ester transfer rate in total plasma. Whereas both human and rabbit apoCI readily associate with HDL, only human apoCI was found to modify the electrostatic charge of HDL. In humans, both CETP and apoCI at normal, physiological levels contribute significantly to the plasma cholesteryl ester transfer rate. In contrast, CETP is the sole major determinant of cholesteryl ester transfer in normolipidemic rabbit plasma as a result of the inability of rabbit apoCI to change HDL electronegativity.