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

Christoffersen, Christina; Jauhiainen, Matti; Moser, Markus; Porse, Bo; Ehnholm, Christian; Boesl, Michael; Dahlbäck, Björn LU and Nielsen, Lars Bo (2008) In Journal of Biological Chemistry 283(4). p.1839-1847
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 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... (More)
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 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 similar to 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
283
issue
4
pages
1839 - 1847
publisher
ASBMB
external identifiers
  • wos:000252501000009
  • scopus:38349149516
ISSN
1083-351X
DOI
10.1074/jbc.M704576200
language
English
LU publication?
yes
id
e123942c-36cb-4f4d-94d8-ce8d34d7c110 (old id 1199030)
date added to LUP
2008-09-10 18:07:59
date last changed
2017-11-19 03:35:15
@article{e123942c-36cb-4f4d-94d8-ce8d34d7c110,
  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 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 similar to 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.},
  author       = {Christoffersen, Christina and Jauhiainen, Matti and Moser, Markus and Porse, Bo and Ehnholm, Christian and Boesl, Michael and Dahlbäck, Björn and Nielsen, Lars Bo},
  issn         = {1083-351X},
  language     = {eng},
  number       = {4},
  pages        = {1839--1847},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice},
  url          = {http://dx.doi.org/10.1074/jbc.M704576200},
  volume       = {283},
  year         = {2008},
}