Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.
Transgenic mouse lines carrying several copies of the mouse apo A-IV gene were produced. Lipoprotein composition and function, and aortic lesion development were examined. Apo A-IV levels in the plasma of transgenic mice were elevated threefold compared with nontransgenic littermates on a chow diet, and sixfold in mice fed an atherogenic diet. Plasma concentrations of total cholesterol, HDL cholesterol, triglycerides, and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0.05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and free fatty acids (P < 0.05), and lower levels of unesterified cholesterol (P < 0.05), than nontransgenic littermates. Expression of the apo A-IV transgene had a protective effect against the formation of diet-induced aortic lesions, with transgenics exhibiting lesion scores of approximately 30% those seen in control mice. HDL-sized lipoproteins isolated from transgenic mice fed the atherogenic diet promoted cholesterol efflux from cholesterol-loaded human monocytes more efficiently than comparable lipoproteins from nontransgenic counterparts. Plasma from transgenics also exhibited higher endogenous cholesterol esterification rates. Taken together, these results suggest that apo A-IV levels influence the metabolism and antiatherogenic properties of HDL.
Cohen
R D
RD
Lipid Research Laboratory, West Los Angeles Veterans Affairs Medical Center, California 90073, USA.
Castellani
L W
LW
Qiao
J H
JH
Van Lenten
B J
BJ
Lusis
A J
AJ
Reue
K
K
D000818:Animals; D001011:Aorta / Q000473:pathology*; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism*; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D015870:Gene Expression; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D001054:Apolipoproteins A; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; D002784:Cholesterol