First Author | Spady DK | Year | 1998 |
Journal | J Biol Chem | Volume | 273 |
Issue | 1 | Pages | 126-32 |
PubMed ID | 9417056 | Mgi Jnum | J:45043 |
Mgi Id | MGI:1101657 | Doi | 10.1074/jbc.273.1.126 |
Citation | Spady DK, et al. (1998) Overexpression of cholesterol 7alpha-hydroxylase (CYP7A) in mice lacking the low density lipoprotein (LDL) receptor gene. LDL transport and plasma LDL concentrations are reduced. J Biol Chem 273(1):126-32 |
abstractText | 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. |