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.
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.
Masson
David
D
Laboratoire de Biochimie des Lipoprotéines, INSERM U498, Faculté de Médecine, BP87900, 21079 Dijon Cedex, France. david.masson@chu-dijon.fr
Pais de Barros
Jean-Paul
JP
Zak
Zoulika
Z
Gautier
Thomas
T
Le Guern
Naig
N
Assem
Mahfoud
M
Chisholm
Jeffrey W
JW
Paterniti
James R
JR
Lagrost
Laurent
L
D000818:Animals; D030801:Animals, Genetically Modified; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D053302:Apolipoprotein C-I; D001056:Apolipoproteins C / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D053302:Apolipoprotein C-I; D001056:Apolipoproteins C; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol