Submitted on July 7, 2005
Revised on October 3, 2005
Accepted on November 9, 2005
Human apolipoprotein AI expression in cholesteryl ester transfer protein (CETP) transgenic rats leads to fewer amounts of apo CI in high density lipoproteins (HDL) and to magnification of CETP-mediated lipoprotein changes
David Masson, Jean-Paul Pais de Barros, Zoulika Zak, Thomas Gautier, Naig Le Guern, Mahfoud Assem, Jeffrey W. Chisholm, James R. Paterniti . Jr, and Laurent Lagrost
Biochemistry Dept., INSERM U498, Dijon, Cedex 21034
Corresponding Author: david.masson{at}laposte.net
Plasma cholesteryl ester transfer protein (CETP) has a profound effect on neutral lipid transfers between high density lipoproteins (HDL) and apoB-containing lipoproteins when it is expressed in combination with human apoAI in HuAI/CETP transgenic (Tg) rodents. In the present study, human apoAI-mediated lipoprotein changes in HuAI/CETPTg rats are characterized by 3 to 5-fold increments in the apoB-containing lipoprotein to HDL cholesterol ratio, and in the cholesteryl ester to triglyceride ratio in apoB-containing lipoproteins. These changes occur despite no change in plasma CETP concentration in HuAI/CETPTg rats as compared to CETPTg rats. A number of HDL apolipoproteins, including rat apoAI and rat apoCI are removed from the HDL surface as a result of human apoAI overexpression. Rat apoCI which is shown to constitute a potent inhibitor of CETP accounts for approximately two thirds of CETP inhibitory activity in HDL from wild-type rats, with the remainder being carried by other HDL-bound apolipoprotein inhibitors. It is concluded that human apoAI overexpression modifies HDL particles in a way that suppresses their ability to inhibit CETP. ApoCI decrease in HDL of HuAI/CETPTg rats contributes chiefly to the loss of the CETP inhibitory potential that is normally associated with wild-type HDL.
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