Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL.
In order to investigate the direct effect of cholesteryl ester transfer protein (CETP) on the structure and composition of HDL in vivo, simian CETP was expressed in Fisher rat that spontaneously displays high plasma levels of HDL1. In the new CETPTg rat line, the production of active CETP by the liver induced a significant 48% decrease in plasma HDL cholesterol, resulting in a 34% decrease in total cholesterol level (P < 0.01 in both cases). Among the various plasma HDL subpopulations, the largest HDL were those mostly affected by CETP, with a 74% decrease in HDL1 versus a significantly weaker 38% decrease in smaller HDL2 (P < 0.0001). Apolipoprotein E (apoE)-containing HDL1 were selectively affected by CETP expression, whereas apoA content of HDL remained unmodified. The reduction in the apoE content of serum HDL observed in CETPTg rats compared to controls (53%, P < 0.02) suggests that apoE in HDL may constitute in vivo a major determinant of their ability to interact with CETP. These results bring new insight into the lack of HDL1 in plasma from CETP-deficient heterozygotes despite their substantial 50% decrease in CETP activity. In addition, they indicate that HDL1 constitute reliable and practicable sensors of very low plasma CETP activity in vivo.
Zak
Zoulika
Z
Département de Physiologie et de Pharmacologie Clinique, CNRS UMR 5014, IFR 39, Université Claude Bernard Lyon I, 69008 Lyon, France.
Lagrost
Laurent
L
Gautier
Thomas
T
Masson
David
D
Deckert
Valérie
V
Duverneuil
Linda
L
De Barros
Jean-Paul Pais
JP
Le Guern
Naig
N
Dumont
Laure
L
Schneider
Martina
M
Risson
Valérie
V
Moulin
Philippe
P
Autran
Delphine
D
Brooker
Gillian
G
Sassard
Jean
J
Bataillard
Alain
A
D000818:Animals; D030801:Animals, Genetically Modified; D001057:Apolipoproteins E / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins; D006579:Heterozygote; D008297:Male; D012333:RNA, Messenger; D051381:Rats; D011916:Rats, Inbred F344
D001057:Apolipoproteins E; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D012333:RNA, Messenger; D002784:Cholesterol