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

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 [H-3]-labeled cholesteryl ester ([H-3]CE), recombinant CETP or CETP inhibitors at 37 degrees C in vitro. Results: The RLP-cholesterol (RLP-C) level increased time-dependently and the amount of R-LP-C increase (Delta RLP-C) by the incubation was ositively correlated with triglyceride (TG) level in plasma (r=0.597, P=0.0070). [H-3]CE in HDL was transferred to RLP fraction under 37 degrees C incubation, and the amount of [H-3]CE transferred to RLP correlated significantly with Delta RLP-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 [H-3]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 [H-3]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. (c) 2006 Elsevier B.V. All rights reserved.