Plasma phospholipid transfer protein activity, a determinant of HDL kinetics in vivo

OBJECTIVE: Phospholipid transfer protein (PLTP) is an important regulator in the transport of surface components of triglyceride-rich lipoprotein (TRL) to high density lipoprotein (HDL) during lipolysis and may therefore play an important role in regulating HDL transport. In this study we investigated the relationship of plasma PLTP activity with HDL metabolism in men. DESIGN AND METHODS: The kinetics of HDL LpA-I and LpA-I:A-II were measured using intravenous administration of [D3]-leucine, gas chromatography-mass spectrometry (GCMS) and a new multicompartmental model for HDL subpopulation kinetics (SAAM II) in 31 men with wide-ranging body mass index (BMI 18-46 kg/m2). Plasma PLTP activity was determined as the transfer of radiolabelled phosphatidylcholine from small unilamellar phosphatidylcholine vesicles to ultracentrifugally isolated HDL. RESULTS: PLTP activity was inversely associated with LpA-I concentration and production rate (PR) after adjusting for insulin resistance (P < 0.05). No significant associations were observed between plasma PLTP activity and LpA-I fractional catabolic rate (FCR). In multivariate analysis, including homeostasis model assessment score (HOMA), triglyceride, cholesteryl ester transfer protein (CETP) activity and PLTP activity, PLTP activity was the only significant determinant of LpA-I concentration and PR (P = 0.020 and P = 0.016, respectively). CONCLUSIONS: Plasma PLTP activity may be a significant, independent determinant of LpA-I kinetics in men, and may contribute to the maintenance of the plasma concentration of these lipoprotein particles in setting of hypercatabolism of HDL.