HDL from rabbits treated with JTT-705 removes cholesterol from macrophages just as efficiently as normal HDL, despite higher CETP-inhibited levels (Atherosclerosis 2002)

Original title: Effect of HDL, from Japanese white rabbit administered a new cholesteryl ester transfer protein inhibitor JTT-705, on cholesteryl ester accumulation induced by acetylated low density lipoprotein in J774 macrophage

Atherosclerosis · 1 May 2002 · 5

Kobayashi J, Okamoto H, Otabe M, Bujo H, Saito Y

Building on an earlier report that the CETP inhibitor JTT-705 is a potentially anti-atherogenic compound, researchers examined how JTT-705 affects HDL properties in Japanese white rabbits, focusing on reverse cholesterol transport in J774 macrophages. Plasma HDL cholesterol, along with HDL2 and HDL3 cholesterol, was significantly higher in JTT-705-treated rabbits than controls on days 3 and 7, while plasma CETP activity stayed lower throughout. Cholesterol efflux from cholesterol ester-loaded J774 macrophages, measured by adding HDL from treated or control rabbits to the culture media, showed comparable cholesterol ester reduction per unit of added HDL in both groups. Since JTT-705-treated rabbits had higher absolute HDL concentrations, the treatment produced a net beneficial effect on macrophage cholesterol removal despite the individual HDL particles functioning no differently than controls.

Original abstract

We have previously reported a potent and specific cholesteryl ester transfer protein (CETP) inhibitor JTT-705 was a potentially anti-atherogenic compound (Nature 406 (2000) 203). In the present study, we investigated in vitro how this compound affects properties of high density lipoprotein (HDL) in Japanese white (JW) rabbits in terms of reverse cholesterol transport in J774 macrophages. Plasma HDL-cholesterol (C) level was significantly higher in the rabbits administered JTT-705 than in control rabbits on days 3 and 7. Both HDL(2) and HDL(3)-C levels were also significantly higher in JTT-705-administered rabbits than in control rabbits. During this period, plasma CETP activity was kept lower in JTT-705-administered rabbits than in controls. To determine how this compound affects the property of HDL particles, we investigated the C efflux induced by HDL from JTT-705-administered and control rabbits in J774 macrophages. Cholesterol ester (CE) concentration in J774 macrophages was reduced in proportion with increasing concentration of the added HDL to the culture media for J774 macrophages in both groups, suggesting that the HDL from JTT-705-administered rabbits was able to reduce CE concentration in J774 macrophages as efficiently as that from control rabbits. This result, together with the finding that the absolute HDL concentration increased in JW rabbits administered this CETP inhibitor, suggests that treatment with this new compound causes a beneficial effect on lipid metabolism in terms of anti-atherogenicity.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.