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J Biol Chem, Vol. 274, Issue 17, 11564-11572, April 23, 1999
Overexpression of Human Apolipoprotein A-II in Mice Induces
Hypertriglyceridemia Due to Defective Very Low Density Lipoprotein
Hydrolysis
Elisabeth
Boisfer ,
Gilles
Lambert ,
Véronique
Atger¶,
Nhuan Quang
Tran ,
Danièle
Pastier ,
Claire
Benetollo ,
Jean-François
Trottier ,
Isabelle
Beaucamps ,
Micheline
Antonucci ,
Michel
Laplaud ,
Sabine
Griglio ,
Jean
Chambaz , and
Athina-Despina
Kalopissis
From Unité 505 INSERM, Institut des Cordeliers,
15, rue de l'Ecole de Médecine, 75006 Paris, the
¶ Laboratoire de Biochimie Hôpital Broussais, 96, rue Didot,
75014 Paris, and Unité 321 INSERM, Hôpital de la
Pitié-Salpêtrière, 83, boulevard de
l'Hôpital, 75013 Paris, France
Two lines of transgenic mice, hAIItg- and
hAIItg- , expressing human apolipoprotein (apo)A-II at 2 and 4 times
the normal concentration, respectively, displayed on standard chow
postprandial chylomicronemia, large quantities of very low density
lipoprotein (VLDL) and low density lipoprotein (LDL) but greatly
reduced high density lipoprotein (HDL). Hypertriglyceridemia may result
from increased VLDL production, decreased VLDL catabolism, or both. Post-Triton VLDL production was comparable in transgenic and control mice. Postheparin lipoprotein lipase (LPL) and hepatic lipase activities decreased at most by 30% in transgenic mice, whereas adipose tissue and muscle LPL activities were unaffected, indicating normal LPL synthesis. However, VLDL-triglyceride hydrolysis by exogenous LPL was considerably slower in transgenic compared with control mice, with the apparent Vmax of the
reaction decreasing proportionately to human apoA-II expression. Human
apoA-II was present in appreciable amounts in the VLDL of transgenic
mice, which also carried apoC-II. The addition of purified apoA-II in postheparin plasma from control mice induced a
dose-dependent decrease in LPL and hepatic lipase
activities. In conclusion, overexpression of human apoA-II in
transgenic mice induced the proatherogenic lipoprotein profile of low
plasma HDL and postprandial hypertriglyceridemia because of decreased
VLDL catabolism by LPL.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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