Okamoto Hiroshi, Miyai Atsuko, Sasase Tomohiko, Furukawa Noboru, Matsushita Mutsuyoshi, Nakano Takamitsu, Nakajima Katsuyuki
Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka, 569-1125, Japan.
Clin Chim Acta. 2007 Jan;375(1-2):92-8. doi: 10.1016/j.cca.2006.06.015. Epub 2006 Jun 20.
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.
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.
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.
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.
胆固醇酯转运蛋白（CETP）被认为与残粒样脂蛋白颗粒（RLP）中的胆固醇水平有关，但尚无直接证据表明CETP会增加血浆中富含胆固醇的RLP。
将人血浆在37℃体外孵育，分别添加或不添加含有[³H]标记胆固醇酯（[³H]CE）的高密度脂蛋白（HDL）、重组CETP或CETP抑制剂。
RLP胆固醇（RLP-C）水平随时间呈依赖性增加，孵育导致的RLP-C增加量（ΔRLP-C）与血浆中甘油三酯（TG）水平呈正相关（r = 0.597，P = 0.0070）。在37℃孵育下，HDL中的[³H]CE转移至RLP组分，转移至RLP的[³H]CE量与血浆中的ΔRLP-C显著相关（r = 0.611，P = 0.0156）。人重组CETP增强了RLP-C的增加，而CETP抑制剂JTT-705和抗人CETP单克隆抗体既抑制了RLP-C的增加，也抑制了[³H]CE向RLP的转移。另一方面，抑制卵磷脂胆固醇酰基转移酶（LCAT）并不影响RLP-C的增加。在富含甘油三酯的脂蛋白（TRL）组分中，JTT-705对[³H]CE向RLP的转移抑制作用比对非RLP的抑制作用更强。
CETP通过将CE从HDL转移至TRL促进富含胆固醇的RLP的形成，CETP抑制剂有助于降低RLP-C。
