Apolipoprotein E enhances lipid exchange between lipoproteins mediated by cholesteryl ester transfer protein.

The direct effect of apolipoprotein (apo) E on cholesteryl ester transfer protein (CETP) activity was studied using lipoproteins from a subject with apoE deficiency (Atherosclerosis. 1991. 88: 15-20) as a model system. The transfer of cholesteryl ester (CE) from discoidal bilayer particles (DBP) to very low density lipoprotein (VLDL) was enhanced by incorporation of apoE into VLDL. This enhancement was induced only in the presence of CETP activity. Moreover, after incubation of CETP with VLDL, CETP activity and immunoreactivity were coeluted with apoE-incorporated VLDL (E-VLDL) on a gel filtration column (Sephadex G-150), but there was little CETP activity and immunoreactivity with apoE-free VLDL (C-VLDL), suggesting that E-VLDL had higher affinity for CETP compared to C-VLDL. The supplementation of the apoE-deficient serum with apoE enhanced the CETP-mediated changes of amount of CE and triglyceride (TG) in the high density lipoprotein (HDL) fraction, which were completely inhibited by the addition of the monoclonal antibody against CETP that blocks CETP activity. Our results suggest that 1) apoE enhances the cholesteryl ester and triglyceride transfer between VLDL and HDL via cholesteryl ester transfer protein, and 2) this effect of apoE may be mediated by enhancing the affinity of CETP for VLDL.