Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice

Christina Christoffersen, Matti Jauhiainen, Markus Moser, Bo Porse, Christian Ehnholm, Michael Boesl, Björn Dahlbäck, Lars Bo Nielsen

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163 Citations (Scopus)

Abstract

To investigate the role of apoM in high density lipoprotein (HDL) metabolism and atherogenesis, we generated human apoM transgenic (apoM-Tg) and apoM-deficient (apoM(-/-)) mice. Plasma apoM was predominantly associated with 10-12-nm alpha-migrating HDL particles. Human apoM overexpression (11-fold) increased plasma cholesterol concentration by 13-22%, whereas apoM deficiency decreased it by 17-21%. The size and charge of apoA-I-containing HDL in plasma were not changed in apoM-Tg or apoM(-/-) mice. However, in plasma incubated at 37 degrees C, lecithin:cholesterol acyltransferase-dependent conversion of alpha- to pre-alpha-migrating HDL was delayed in apoM-Tg mice. Moreover, lecithin: cholesterol acyltransferase-independent generation of pre-beta-migrating apoA-I-containing particles in plasma was increased in apoM-Tg mice (4.2 +/- 1.1%, p = 0.06) and decreased in apoM(-/-) mice (0.5 +/- 0.3%, p = 0.03) versus controls (1.8 +/- 0.05%). In the setting of low density lipoprotein receptor deficiency, apoM-Tg mice with approximately 2-fold increased plasma apoM concentrations developed smaller atherosclerotic lesions than controls. The effect of apoM on atherosclerosis may be facilitated by enzymatic modulation of plasma HDL particles, increased cholesterol efflux from foam cells, and an antioxidative effect of apoM-containing HDL.
Original languageEnglish
JournalThe Journal of Biological Chemistry
Volume283
Issue number4
Pages (from-to)1839-47
Number of pages9
ISSN0021-9258
DOIs
Publication statusPublished - 25 Jan 2008

Keywords

  • Animals
  • Antioxidants
  • Apolipoprotein A-I
  • Apolipoproteins
  • Atherosclerosis
  • Cholesterol
  • Foam Cells
  • Gene Expression
  • Humans
  • Lipocalins
  • Lipoproteins, HDL
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Receptors, LDL

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