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

Cholesteryl ester transfer protein (CETP) plays a controversial role in ath erogenesis by contributing to the net transfer of high density lipoprotein (HDL) cholesteryl ester (CE) to the liver via apolipoprotein-B-containing l ipoproteins (apoB-LP). We evaluated in vitro the CETP-mediated bidirectiona l transfer of CE from HDL to the chemically modified pro-atherogenic low de nsity lipoprotein (LDL) particles. Acetylated or oxidized (ox) LDL. either unlabeled or [H-3]-CE labeled. were incubated with [C-14]-CE-HDL in the pre sence of the lipoprotein-deficient plasma fraction (d>1.21 g/ml) as the sou rce of CETP. The amount of radioactive CE transferred was determined after dextran sulfate/MgCl2, precipitation of LDL. The results showed a 1.4-2.8-f old lower HDL-CE transfer to acetylated LDL while no effect was: observed o n the CE transfer to oxidized LDL. However. the reverse transfer rate of [H -3]CE-LDL to HDL was 1.4-3.6 times greater when LDL was oxidized than when it was intact. Overall, HDL, was better than HDL, as donor of CE to native LDL. probably reflecting the relatively greater CE content of HDL2. Oxidati on 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. (C) 2001 Elsevier Science B.V. All rights reserved.