The LDL receptor plays a critical role in the regulation of
of LDL clearance (13). Loss of LDL receptor function
leads to decreased LDL catabolism and elevated LDL lev-
els (4). LDL receptor levels are affected by diet, hormones,
locus that lead to familial hypercholesterolemia (FH).
Early studies of LDL metabolism in patients with FH
overproduce LDL (5, 6) and relatively small VLDL parti-
cles (7). VLDL is the metabolic precursor of LDL and is
converted to LDL through the action of lipoprotein
lipase, a triacylglycerol lipase that acts upon VLDL while
it circulates in the bloodstream (8). Increased production
of VLDL can lead to increased LDL simply by providing
more precursor. In addition, impaired clearance of VLDL
remnants can lead to LDL overproduction (9).
A long-standing paradox in the lipoprotein field is
posed by the cholesterol-lowering drugs known as