In vivo stable-isotope kinetic study suggests intracellular assembly of lipoprotein(a)

ObjectiveLipoprotein(a) [Lp(a)] consists of apolipoprotein B-100 (apoB-100) as part of an LDL-like particle and the covalently linked glycoprotein apolipoprotein(a) [apo(a)]. Detailed mechanisms of its biosynthesis, assembly, secretion and catabolism are still poorly understood. To address the Lp(a) assembly mechanism, we studied the in vivo kinetics of apo(a) and apoB-100 from Lp(a) and LDL apoB-100 in nine healthy probands using stable-isotope methodology.MethodsThe level of isotope enrichment was used to calculate the fractional synthesis rate (FSR), production rate (PR) and retention time (RT) using SAAMII software and multicompartmental modeling.ResultsWe observed a similar mean PR for apo(a) (1.15 nmol/kg/d) and apoB-100 (1.31 nmol/kg/d) from Lp(a), which differed significantly from the PR for apoB-100 from LDL (32.6 nmol/kg/d). Accordingly, mean FSR and RT values for Lp(a)-apo(a) were similar to those of Lp(a)-apoB and different from those for LDL-apoB.ConclusionTwo different kinetic apoB pools within Lp(a) and LDL suggest intracellular Lp(a) assembly from apo(a) and newly synthesized LDL.

► Assembly mechanisms of the atherogenic lipoprotein Lp(a) were investigated. ► Kinetic study was performed in healthy human subjects using stable isotopes. ► Obtained metabolic parameters are compatible with intracellular assembly of Lp(a).