Oxidation of LDL enhances the cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester transfer rate to HDL, bringing on a diminished net transfer of cholesteryl ester from HDL to oxidized LDL

Cholesteryl ester transfer protein (CETP) plays a controversial role in atherogenesis by contributing to the net transfer of high density lipoprotein (HDL) cholesteryl ester (CE) to the liver via apolipoprotein-B-containing lipoproteins (apoB-LP). We evaluated in vitro the CETP-mediated bidirectional transfer of CE from HDL to the chemically modified pro-atherogenic low density lipoprotein (LDL) particles. Acetylated or oxidized (ox) LDL, either unlabeled or [ 3H]-CE labeled, were incubated with [ 14C]-CE-HDL in the presence of the lipoprotein-deficient plasma fraction ( d>1.21 g/ml) as the source of CETP. The amount of radioactive CE transferred was determined after dextran sulfate/MgCl 2 precipitation of LDL. The results showed a 1.4–2.8-fold lower HDL-CE transfer to acetylated LDL while no effect was observed on the CE transfer to oxidized LDL. However, the reverse transfer rate of [ 3H]CE-LDL to HDL was 1.4–3.6 times greater when LDL was oxidized than when it was intact. Overall, HDL 2 was better than HDL 3 as donor of CE to native LDL, probably reflecting the relatively greater CE content of HDL 2. Oxidation of LDL enhanced the CETP-mediated cholesteryl ester transfer rate to HDL, bringing on a reduced net transfer rate of cholesteryl ester from HDL to ox LDL. This may diminish the oxLDL particle’s atherogenic effect.