Lipoprotein metabolism in familial hypercholesterolemia.

Low density lipoprotein (LDL) receptor deficiency, which causes homozygous familial hypercholesterolemia (FH), is accompanied by a gross disturbance in the metabolism of apolipoprotein (apo) B-containing lipoproteins. Not only is plasma LDL increased, but also the less dense lipoproteins (of very low and intermediate density) accumulate to a similar extent. Only the largest triglyceride-rich subfraction of very low density lipoprotein (VLDL) is not affected. The metabolic disturbance is characterized by oversynthesis of apo B and a defect in its clearance along the length of the delipidation cascade from VLDL to LDL. This phenomenon leads to delayed transit of particles through the system, extending the residence time of the B protein in the plasma by three- to fourfold. Receptor deficiency, therefore, results in accumulation of a number of lipoprotein species that have been implicated in the pathogenesis of atherosclerosis.