CHOLESTEROL EFFLUX POTENTIAL OF SERA FROM MICE EXPRESSING HUMAN CHOLESTERYL ESTER TRANSFER PROTEIN AND OR HUMAN APOLIPOPROTEIN AL/

The ability of whole serum to promote cell cholesterol efflux and the relationships between apoprotein and lipoprotein components of human s erum and efflux have been investigated previously (de la Llera Moya, M ., V. Atger. J. L. Paul, N. Fournier, N. Moatti, P. Giral, K. E. Frida y, and G. H. Rothblat, 1994. Arterioscler, Thromb. 14:1056-1065), We h ave now used this experimental system to study the selective effects o f two human lipoprotein-related proteins, apoprotein AI (ape AI) and c holesteryl ester transfer protein (CETP) on cell cholesterol efflux, w hen these proteins are expressed in transgenic mice, The percent efflu x 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 ape AI transgenic (HuAITg) > human CETP transgenic (HuCETPTg) > human ape AI and CETP transgenic (HuAICETPTg) much greater than apo A I knockout mice, In each group of mice a strong, positive correlation (r(2) ranging from 0.64 to 0.76) was found between efflux and HDL chol esterol concentrations, The slopes of these regression lines differed between groups of mice, indicating that the cholesterol acceptor effic iencies of the sera differed among groups, These differences in relati ve efficiencies can explain why cholesterol efflux was not proportiona l to the different HDL levels in the various groups of mice, We can co nclude that: (a) HDL particles from HuAITg mice are less efficient as cholesterol accepters 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 backgro und mice; and (c) the coexpression of both human ape AI and CETP impro ves the efficiency of HDL particles in the HuAICETPTg mice when compar ed with the HuAITg mice, We also demonstrated that the esterification of the free cholesterol released from the cells by lecithin cholestero l acyltransferase in the serum was reduced in the HuAITg and AI knocko ut mice, whereas it was not different from background values in the tw o groups of mice expressing human CETP.