Faculty Collaboration Database

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. J Lipid Res 2006 Feb;47(2):356-65

Date

11/12/2005

Pubmed ID

16282639

DOI

10.1194/jlr.M500288-JLR200

Scopus ID

2-s2.0-33244471515 (requires institutional sign-in at Scopus site)   6 Citations

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.

Author List

Masson D, Pais de Barros JP, Zak Z, Gautier T, Le Guern N, Assem M, Chisholm JW, Paterniti JR Jr, Lagrost L

Author

Mahfoud Assem PharmD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Genetically Modified
Apolipoprotein A-I
Apolipoprotein C-I
Apolipoproteins C
Carrier Proteins
Cholesterol
Cholesterol Ester Transfer Proteins
Cholesterol Esters
Gene Expression
Glycoproteins
Haplorhini
Humans
Lipoproteins
Lipoproteins, HDL
Lipoproteins, LDL
Lipoproteins, VLDL
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Triglycerides