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Vol. 273, Issue 1, 126-132, January 2, 1998
-Hydroxylase (CYP7A) in Mice
Lacking the Low Density Lipoprotein (LDL) Receptor Gene
From the Department of Internal Medicine, University of Texas
Southwestern Medical Center, Dallas, Texas 75235-8887
This study was undertaken to determine the effect
of transient overexpression of hepatic cholesterol 7
-hydroxylase on
low density lipoprotein (LDL) cholesterol transport in mice lacking LDL
receptors (LDL receptor
/). Primary overexpression
of hepatic 7-hydroxylase in LDL receptor/ mice
was accompanied by a dose-dependent decrease in the rate of
LDL cholesterol appearance in plasma (whole body LDL cholesterol transport) and a corresponding reduction in circulating LDL cholesterol levels. The increase in hepatic 7-hydroxylase activity necessary to
achieve a 50% reduction in plasma LDL cholesterol concentrations was
~10-fold. In comparison, cholestyramine increased hepatic 7-hydroxylase activity ~3-fold and reduced plasma LDL cholesterol concentrations by 17%. This study demonstrates that augmentation of
hepatic 7-hydroxylase expression is an effective strategy for
lowering plasma LDL concentrations even in animals with a genetic
absence of LDL receptors.
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