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 [(3)H]-labeled cholesteryl ester ([(3)H]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 RLP-C increase (DeltaRLP-C) by the incubation was positively correlated with triglyceride (TG) level in plasma (r=0.597, P=0.0070). [(3)H]CE in HDL was transferred to RLP fraction under 37 degrees C incubation, and the amount of [(3)H]CE transferred to RLP correlated significantly with DeltaRLP-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 [(3)H]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 [(3)H]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.
Okamoto
Hiroshi
H
Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka, 569-1125, Japan. hiroshi.okamoto@ims.jti.co.jp
Miyai
Atsuko
A
Sasase
Tomohiko
T
Furukawa
Noboru
N
Matsushita
Mutsuyoshi
M
Nakano
Takamitsu
T
Nakajima
Katsuyuki
K
D000577:Amides; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004952:Esters; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*
D000577:Amides; D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D004791:Enzyme Inhibitors; D004952:Esters; D008074:Lipoproteins; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; D014280:Triglycerides; C112017:remnant-like particle cholesterol; C411602:dalcetrapib; D002784:Cholesterol; D004228:Dithionitrobenzoic Acid; D007862:Phosphatidylcholine-Sterol O-Acyltransferase