HDL particles from CETP-transgenic mice are more efficient cholesterol acceptors than from apoA-I-only transgenic mice, despite lower HDL levels (J Clin Invest 1995)

Original title: Cholesterol efflux potential of sera from mice expressing human cholesteryl ester transfer protein and/or human apolipoprotein AI

J Clin Invest · 1 December 1995 · 7

Atger V, de la Llera Moya M, Bamberger M, Francone O, Cosgrove P, Tall A, Walsh A, Moatti N, Rothblat G

Building on a prior whole-serum cholesterol efflux assay system, this study examined the selective effects of human apoA-I and CETP, expressed as transgenes in mice, on cell cholesterol efflux. Percent cholesterol efflux from Fu5AH donor cells to 5% sera followed the order: background = human apoA-I transgenic (HuAITg) > human CETP transgenic (HuCETPTg) > human apoA-I and CETP transgenic (HuAICETPTg) >> apoA-I knockout mice, with a strong positive correlation (r2 0.64 to 0.76) between efflux and HDL cholesterol in each group, though regression slopes differed. HDL from HuAITg mice was a less efficient acceptor than background HDL, while HDL from HuCETPTg mice was more efficient than background HDL despite lower HDL cholesterol, and coexpressing apoA-I and CETP improved HDL efficiency over HuAITg alone.

Original abstract

The ability of whole serum to promote cell cholesterol efflux and the relationships between apoprotein and lipoprotein components of human serum efflux have been investigated previously (de la Llera Moya, M., V. Atger, J.L. Paul, N. Fournier, N. Moatti, P. Giral, K.E. Friday, and G.H. Rothblat. 1994. Arterioscler. Thromb. 14:1056-1065). We have now used this experimental system to study the selective effects of two human lipoprotein-related proteins, apoprotein AI (apo AI) and cholesteryl ester transfer protein (CETP) on cell cholesterol efflux, when these proteins are expressed in transgenic mice. The percent efflux values for cholesterol released in 4 h from Fu5AH donor cells to 5% sera from the different groups of mice were in the order: background = human apo AI transgenic (HuAITg) > human CETP transgenic (HuCETPTg) > human apo AI and CETP transgenic (HuAICETPTg) >> apo AI knockout mice. In each group of mice a strong, positive correlation (r2 ranging from 0.64 to 0.76) was found between efflux and HDL cholesterol concentrations. The slopes of these regression lines differed between groups of mice, indicating that the cholesterol acceptor efficiencies of the sera differed among groups. These differences in relative efficiencies can explain why cholesterol efflux was not proportional to the different HDL levels in the various groups of mice. We can conclude that: (a) HDL particles from HuAITg mice are less efficient as cholesterol acceptors than HDL from the background mice; (b) despite a lower average efflux due to lower HDL cholesterol concentrations, HDL particles are more efficient in the HuCETPTg mice than in the background mice; and (c) the coexpression of both human apo AI and CETP improves the efficiency of HDL particles in the HuAICETPTg mice when compared with the HuAITg mice. We also demonstrated that the esterification of the free cholesterol released from the cells by lecithin cholesterol acyltransferase in the serum was reduced in the HuAITg and AI knockout mice, whereas it was not different from background values in the two groups of mice expressing human CETP.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.