HDL biology
CETP shuttles oxidized cholesteryl linoleate between LDL and HDL without distinguishing it from the unoxidized form (J Lipid Res 1995)
Original title: Exchange of oxidized cholesteryl linoleate between LDL and HDL mediated by cholesteryl ester transfer protein
This study examined CETP-mediated exchange of oxidized cholesteryl linoleate species, the hydroperoxide (Ch18:2-OOH) and hydroxide (Ch18:2-OH) forms, between LDL and HDL. When labeled oxidized LDL was incubated with unoxidized HDL and purified CETP, both oxidized species accumulated in HDL, and the reverse direction (labeled oxidized HDL to unoxidized LDL) produced comparable accumulation in LDL; transfer rates for oxidized cholesteryl linoleate to HDL were comparable to those for the unoxidized form. The rate of transfer from LDL to HDL increased linearly as the HDL to oxidized-LDL molar ratio rose from 0.5:1 to 10:1, accompanied by a shift toward more of the oxidized lipid being present as the hydroxide rather than hydroperoxide form, though further increases in this ratio had no additional effect. The authors conclude that CETP mediates bidirectional transfer of both oxidized cholesteryl linoleate species without distinguishing them from the unoxidized form, and that association with HDL accelerates reduction of the hydroperoxide to the hydroxide.
Original abstract
This study examines the cholesteryl ester transfer protein (CETP)-mediated exchange of cholesteryl linoleate hydroperoxide (Ch18:2-OOH) and cholesteryl linoleate hydroxide (Ch18:2-OH) between low density lipoprotein (LDL) and high density lipoprotein (HDL). When [3H]Ch18:2-OOH- and [3H]18:2-OH-labeled LDL were incubated at 37 degrees C for 0-24 h with unoxidized HDL and purified CETP, Ch18:2-OOH and Ch18:2-OH accumulated in the HDL. Similarly, when incubations were carried out with [3H]Ch18:2-OOH- and [3H]Ch18:2-OH-labeled HDL, unoxidized LDL, and CETP, Ch18:2-OOH and Ch18:2-OH accumulated in the LDL. Comparable results were obtained for the CETP-mediated transfer of [3H]Ch18:2-OH alone from LDL to HDL. Transfer to HDL of oxidized cholesteryl linoleate from [3H]Ch18:2-OOH- and [3H]Ch18:2-OH-labeled LDL was comparable to that of unoxidized cholesteryl linoleate (Ch18:2). However, the rate of transfer of [3H]Ch18:2-OOH and [3H]Ch18:2-OH from LDL to HDL increased linearly as the molar ratio of acceptor (HDL) to donor (oxidized LDL) particles in the incubation increased from 0.5:1 to 10:1. This increased rate of exchange was accompanied by an increased proportion of the oxidized Ch18:2 being present as the hydroxide rather than hydroperoxide. Further increases in the molar ratio of HDL to oxidized LDL particles neither affected the transfer rate nor the extent of reduction of Ch18:2-OOH to Ch18:2-OH. We therefore conclude that i) CETP mediates bidirectional transfers of Ch18:2-OOH and Ch18:2-OH between HDL and LDL; ii) CETP does not distinguish between Ch18:2-OOH, Ch18:2-OH, and Ch18:2 as it mediates their exchange between HDL and LDL; and iii) association with HDL hastens the reduction of Ch18:2-OOH to Ch18:2-OH.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.