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The Journal of Lipid Research, Vol. 40, 1064-1070, June 1999
Copyright © 1999 by Lipid Research, Inc.
ApoA-II maintains HDL levels in part by inhibition of hepatic lipase: studies in apoA-II and hepatic lipase double knockout mice
Wei Wenga,
Neal A. Brandenburga,
Shaobin Zhongb,
Joanna Halkiasa,
Lin Wua,
Xian-cheng Jiangb,
Alan Tallb, and
Jan L. Breslowa
a Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, 1230 York Avenue, New York, NY 10021
b Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032
Correspondence to:
Jan L. Breslow
High density lipoprotein (HDL) cholesterol levels are inversely related to the risk of developing coronary heart disease. Apolipoprotein (apo) A-II is the second most abundant HDL apolipoprotein and apoA-II knockout mice show a 70% reduction in HDL cholesterol levels. There is also evidence, using human apoA-II transgenic mice, that apoA-II can prevent hepatic lipase-mediated HDL triglyceride hydrolysis and reduction in HDL size. These observations suggest the hypothesis that apoA-II maintains HDL levels, at least in part, by inhibiting hepatic lipase. To evaluate this, apoA-II knockout mice were crossbred with hepatic lipase knockout mice. Compared to apoA-II-deficient mice, in double knockout mice there were increased HDL cholesterol levels (57% in males and 60% in females), increased HDL size, and decreased HDL cholesteryl ester fractional catabolic rate. In vitro incubation studies of plasma from apoA-II knockout mice, which contains largely apoA-I HDL particles, showed active lipolysis of HDL triglyceride, whereas similar studies of plasma from apoA-I knockout mice, which contains largely apoA-II particles, did not..
In summary, these results strongly suggest that apoA-II is a physiological inhibitor of hepatic lipase and that this is at least part of the mechanism whereby apoA-II maintains HDL cholesterol levels.Weng, W., N. A. Brandenburg, S. Zhong, J. Halkias, L. Wu, X-c. Jiang, A. Tall, and J. L. Breslow. ApoA-II maintains HDL levels in part by inhibition of hepatic lipase: studies in apoA-II and hepatic lipase double knockout mice. J. Lipid Res. 1999. 40: 10641070.
Supplementary key words:
apoA-II , apoA-I , hepatic lipase , HDL cholesterol

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