Human apolipoprotein A-II determines plasma triglycerides by regulating lipoprotein lipase activity and high-density lipoprotein proteome

Josep Julve, Joan Carles Escolà-Gil, Noemi Rotllan, Catherine Fiévet, Emmanuelle Vallez, Carolina De La Torre, Vicent Ribas, John H. Sloan, Francisco Blanco-Vaca

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57 Citations (Scopus)

Abstract

INTRODUCTION-: Apolipoprotein (apo) A-II is the second most abundant high-density lipoprotein (HDL) apolipoprotein. We assessed the mechanism involved in the altered postprandial triglyceride-rich lipoprotein metabolism of female human apoA-II-transgenic mice (hapoA-II-Tg mice), which results in up to an 11-fold increase in plasma triglyceride concentration. The relationships between apoA-II, HDL composition, and lipoprotein lipase (LPL) activity were also analyzed in a group of normolipidemic women. METHODS AND RESULTS-: Triglyceride-rich lipoprotein catabolism was decreased in hapoA-II-Tg mice compared to control mice. This suggests that hapoA-II, which was mainly associated with HDL during fasting and postprandially, impairs triglyceride-rich lipoprotein lipolysis. HDL isolated from hapoA-II-Tg mice impaired bovine LPL activity. Two-dimensional gel electrophoresis, mass spectrometry, and immunonephelometry identified a marked deficiency in the HDL content of apoA-I, apoC-III, and apoE in these mice. In normolipidemic women, apoA-II concentration was directly correlated with plasma triglyceride and inversely correlated with HDL-to-apoC-II+apoE/apoC-III ratios. HDL-mediated induction of LPL activity was inversely correlated with apoA-II and directly correlated with HDL-to-apoC-II+apoE/apoC-III ratios. Purified hapoA-II displaced apoC-II, apoC-III, and apoE from human HDL2. Human HDL3 was, compared to HDL2, enriched in apoA-II but poorer in apoC-II, apoC-III, and apoE. CONCLUSION-: ApoA-II plays a crucial role in triglyceride catabolism by regulating LPL activity, at least in part, through HDL proteome modulation. © 2010 American Heart Association, Inc.
Original languageEnglish
Pages (from-to)232-238
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number2
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Chylomicron
  • Lipolysis
  • Proteomics
  • Transgenic mice
  • VLDL

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