Low density lipoprotein metabolism in the normal to moderately elevated range of plasma cholesterol: comparisons with...

Low density lipoprotein (LDL) metabolism was investigated using a pulse injection of 125I-labeled LDL in 20 subjects who did not have familial hypercholesterolemia (FH) (plasma cholesterol 160-297 mg/dl) and in 9 subjects who did have heterozygous FH (plasma cholesterol 273-501 mg/dl). Subjects were also injected with 131I-labeled LDL chemically modified with cyclohexanedione. This technique permitted a calculation of the amount of apoLDL removed via receptor-mediated and receptor-independent pathways. In subjects without FH, 40% (range 25-49%) of LDL was cleared via receptor-mediated pathways and in subjects with FH this figure was 22% (range 3-33%). In nonfamilial hypercholesterolemia there was clear evidence of defective removal of LDL via receptor-independent pathways in association with some overproduction of apoLDL. In heterozygous FH there was evidence of defective removal of LDL via receptor-mediated pathways, while some subjects also showed evidence of overproduction of apoLDL. It is suggested that LDL catabolism via receptor-independent pathways plays a major role in regulating plasma cholesterol levels in the normal to moderately elevated range.