Decreased susceptibility to diet-induced atherosclerosis in human apolipoprotein A-II transgenic mice.
Studies performed in vivo have been controversial regarding the implication of human apolipoprotein (apo)A-II in the atherogenic process. Expression of human apoA-II in transgenic mice fed a chow diet leads to (1) a bimodal distribution of high density lipoprotein (HDL) size as in humans, (2) a reduction in total cholesterol concentration that is mainly due to a reduction in non-HDL cholesterol level, and (3) a dramatic reduction in mouse endogenous apoA-I and apoA-II. After 20 weeks on an atherogenic diet, transgenic mice had reduced total cholesterol concentrations because of a reduction in cholesterol associated with all lipoprotein classes. Endogenous apoA-I and apoA-II were also dramatically decreased in transgenic mice. The mean area of atherosclerotic lesions was drastically decreased in transgenic mice (-44%, P=0.0027) compared with control mice. The amount of aortic surface covered by lesions was positively correlated with very low density lipoprotein cholesterol (P<0.01) and intermediate density lipoprotein cholesterol levels (P<0.05). Transgenic mice were protected against the development of atherosclerosis despite a marked decrease in HDL cholesterol and apoA-I concentrations. This protection may be related to the marked reduction in circulating low density lipoprotein (very low density and intermediate density lipoprotein) levels in transgenic mice.
Tailleux
A
A
Département d'athérosclérose et INSERM U. 325 Institut Pasteur, Lille, France. Anne.Tailleux@pasteur-lille.fr
Bouly
M
M
Luc
G
G
Castro
G
G
Caillaud
J M
JM
Hennuyer
N
N
Poulain
P
P
Fruchart
J C
JC
Duverger
N
N
Fiévet
C
C
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics*; D001053:Apolipoproteins / Q000097:blood; D001161:Arteriosclerosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000737:chemistry; D004036:Diet, Atherogenic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D012709:Serum Albumin
D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008055:Lipids; D012709:Serum Albumin; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008071:Lipoprotein Lipase