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Human apoA-I overexpression strips apoC-I from HDL and removes most of HDL's natural CETP-inhibitory capacity in transgenic rats (J Lipid Res 2005)
Original title: Human apoA-I expression in CETP transgenic rats leads to lower levels of apoC-I in HDL and to magnification of CETP-mediated lipoprotein changes
In rats co-expressing human apoA-I and CETP, human apoA-I overexpression amplified CETP-driven lipoprotein changes, producing 3- to 5-fold increases in the apoB-containing lipoprotein to HDL cholesterol ratio and in the cholesteryl ester to triglyceride ratio within apoB-containing lipoproteins, despite unchanged plasma CETP concentration. This occurred because human apoA-I overexpression displaced several HDL apolipoproteins from the particle surface, including rat apoC-I, which normally accounts for roughly two-thirds of the CETP-inhibitory activity carried by wild-type rat HDL. The loss of HDL-bound apoC-I largely explains why human apoA-I overexpression suppresses HDL's natural ability to inhibit CETP, magnifying CETP's lipid-transfer effects.
Original abstract
Plasma cholesteryl ester transfer protein (CETP) has a profound effect on neutral lipid transfers between HDLs and apolipoprotein B (apoB)-containing lipoproteins when it is expressed in combination with human apoA-I in HuAI/CETP transgenic (Tg) rodents. In the present study, human apoA-I-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 with CETPTg rats. A number of HDL apolipoproteins, including rat apoA-I and rat apoC-I are removed from the HDL surface as a result of human apoA-I overexpression. Rat apoC-I, which is known to constitute a potent inhibitor of CETP, accounts for approximately two-thirds of CETP inhibitory activity in HDL from wild-type rats, and the remainder is carried by other HDL-bound apolipoprotein inhibitors. It is concluded that human apoA-I overexpression modifies HDL particles in a way that suppresses their ability to inhibit CETP. An apoC-I 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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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.