Cholesteryl ester transfer protein promotes the formation of cholesterol-rich remnant like lipoprotein particles in human plasma

Abstract

Background Cholesteryl ester transfer protein (CETP) is suggested to be involved in the cholesterol level in remnant like lipoprotein particles (RLP), but there is no direct evidence that CETP increases cholesterol-rich RLP in plasma. Methods Human plasma was incubated with or without HDL containing [ 3H]-labeled cholesteryl ester ([ 3H]CE), recombinant CETP or CETP inhibitors at 37 °C in vitro. Results The RLP–cholesterol (RLP–C) level increased time-dependently and the amount of RLP–C increase ( ΔRLP–C) by the incubation was positively correlated with triglyceride (TG) level in plasma ( r = 0.597, P = 0.0070). [ 3H]CE in HDL was transferred to RLP fraction under 37 °C incubation, and the amount of [ 3H]CE transferred to RLP correlated significantly with ΔRLP–C in plasma ( r = 0.611, P = 0.0156). Human recombinant CETP enhanced the RLP–C increase, while CETP inhibitor JTT-705 and anti-human CETP monoclonal antibody inhibited both the RLP–C increase and [ 3H]CE transfer to RLP. On the other hand, an inhibition of lecithin: cholesterol acyltransferase (LCAT) did not affect the RLP–C increase. In triglyceride-rich lipoproteins (TRL) fraction, JTT-705 inhibited [ 3H]CE transfer to RLP more strongly than that to non-RLP. Conclusions CETP promotes the formation of cholesterol-rich RLP through the transfer of CE from HDL to TRL and CETP inhibitors are useful to reduce RLP–C.