Lipoprotein, Lp(a), is an atherogenic lipoprotein containing both apoB and apo(a) and is similar in structure to LDL. The role of the LDL receptor in the catabolism of Lp(a), and hence the role of Lp(a) in the regulation of cholesterol hemostasis and atherosclerosis, was controversial until the metabolism of purified 125I-Lp(a) and 131I-LDL was simultaneously studied in homozygous FH patients, their heterozygous FH parents, and control subjects to examine the role of LDL receptors in Lp(a) metabolism. The Fractional Catabolic Rate (FCR) of LDL was markedly decreased in the homozygous patients, significantly decreased in the heterozygous patients compared to the controls. In contrast, the FCR of Lp(a) was not significantly different in homozygous or heterozygous patients. This establishes that a reduction in functional LDL receptors does not result in delayed catabolism of Lp(a), indicating that the LDL receptor is not a physiologically important route of Lp(a) catabolism. In subjects studied with a bolus-injected 3H-leucine tracer, or studied similarly with 2H-leucine tracer, or studied by primed constant infusion of 2H-leucine, the rapidly turning-over apoAI fraction, previously hypothesized, could be resolved. The study permitted resolution of ApoAI into two pools, the rapidly appearing faster decaying and the slower decaying following a delay of nearly 12 hours. The slower pool comprises the predominant mass of apoAI found in human fasting plasma; however, the quantity of apoAI transported through the faster pathway was greater than that transported through the slower pathway. This has significant consequences for the measurement of reverse cholesterol transport.
