High Low Density Lipoprotein (LDL) cholesterol 
levels are well-known to cause atherosclerotic diseases. The 
hepatic LDL receptor is the major determinant of plasma 
LDL-cholesterol levels, and as a result, a greater 
understanding of the regulatory mechanisms that control the 
expression and function of this gene is essential. Herein, we 
decided to examine whether the function of the LDL 
receptor increased in response to the cholesterol 
biosynthesis inhibitor, Zaragozic Acid A (ZA), which has 
been shown to significantly decrease serum cholesterol 
levels in rats.  The results demonstrated that ZA increased 
the binding and internalization of Very Low Density 
Lipoprotein (VLDL), but not of LDL. This ZA-dependent 
increase in the internalization rate of VLDL was unrelated 
to an increase in the overall expression levels of the LDL 
receptor at the cell surface. These results suggest that ZA 
could reduce plasma cholesterol levels by preventing the 
synthesis of LDL from VLDL.