title: Overexpression of cholesterol 7alpha-hydroxylase (CYP7A) in mice lacking the low density lipoprotein (LDL) receptor gene. LDL transport and plasma LDL concentrations are reduced.
abstract: This study was undertaken to determine the effect of transient overexpression of hepatic cholesterol 7alpha-hydroxylase on low density lipoprotein (LDL) cholesterol transport in mice lacking LDL receptors (LDL receptor-/-). Primary overexpression of hepatic 7alpha-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 7alpha-hydroxylase activity necessary to achieve a 50% reduction in plasma LDL cholesterol concentrations was approximately 10-fold. In comparison, cholestyramine increased hepatic 7alpha-hydroxylase activity approximately 3-fold and reduced plasma LDL cholesterol concentrations by 17%. This study demonstrates that augmentation of hepatic 7alpha-hydroxylase expression is an effective strategy for lowering plasma LDL concentrations even in animals with a genetic absence of LDL receptors.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235-8887, USA. spady@utsw.swmed.edu
authors.forename: D K
authors.initials: DK
authors.lastname: Spady
authors.forename: J A
authors.initials: JA
authors.lastname: Cuthbert
authors.forename: M N
authors.initials: MN
authors.lastname: Willard
authors.forename: R S
authors.initials: RS
authors.lastname: Meidell
mesh_terms: D000818:Animals; D001692:Biological Transport; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002790:Cholesterol 7-alpha-Hydroxylase