HDL biology
LDL oxidation redirects CETP transfer backward, pulling cholesteryl ester out of LDL and into HDL instead (Clin Chim Acta 2001)
Original title: 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
Testing CETP-mediated bidirectional cholesteryl ester (CE) transfer between HDL and chemically modified LDL in vitro, using lipoprotein-deficient plasma as the CETP source, acetylated LDL showed 1.4-2.8-fold lower CE uptake from HDL than native LDL, while oxidized LDL showed no change in forward CE uptake. However, the reverse transfer rate, from LDL to HDL, was 1.4-3.6 times greater when LDL was oxidized than when intact, and HDL2 was a better CE donor to native LDL than HDL3, reflecting its higher CE content. LDL oxidation thus enhances CETP-mediated CE transfer toward HDL, reducing the net movement of cholesteryl ester from HDL into oxidized LDL, potentially blunting the oxidized particle's atherogenic effect.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.