Abstract 614: Distinct Metabolism of Apo(a) and ApoB-100 Within Plasma Lp(a)

Abstract

Lipoprotein(a) [Lp(a)] is a lipoprotein similar in lipid content and composition to LDL but different in having apolipoprotein (apo) (a) covalently linked to apoB-100. Apo(a) is a heavily glycosylated protein and highly polymorphic in size. The metabolism of apo(a) and apoB-100 within Lp(a) as reported in previous studies is not clear, due in part to differences in methodology and study design among the different studies. We determined the kinetics of apo(a) and apoB-100 within plasma Lp(a) in five male subjects with dyslipidemia [Lp(a) concentration: 8.9-183.5 nmol/l] during a primed constant infusion of [5,5,5- 2 H 3 ] L-leucine, in the constantly fed state. Lp(a) was immunoprecipitated directly from whole plasma, and apo(a) and apoB-100 in Lp(a) were separated by gradient gel electrophoresis. The kinetics of each apolipoprotein was determined by gas chromatography-mass spectrometry and multicompartmental modeling. Apo(a) was found to have a plasma residence time more than twice that of apoB-100 in Lp(a). The fractional catabolic rates of Lp(a)-apo(a) and Lp(a)-apoB-100 were 0.11 ± 0.02 and 0.29 ± 0.06 pools/day, respectively (mean ± SEM; P = 0.04). The median apo(a) production rate (0.248 nmol/kg·day -1 ) was significantly lower than that of Lp(a)-apoB-100 (0.514 nmol/kg·day -1 ; P = 0.03). Our data support the concept that apo(a) and apoB-100 in plasma Lp(a) are catabolized differently in humans in the fed state. We hypothesize that apo(a) does not remain bound to a single apoB-100-containing lipoprotein but, rather, reassociates at least once with another apoB-100-containing particle during its plasma residence.