Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1199030
- author
- Christoffersen, Christina ; Jauhiainen, Matti ; Moser, Markus ; Porse, Bo ; Ehnholm, Christian ; Boesl, Michael ; Dahlbäck, Björn LU and Nielsen, Lars Bo
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 283
- issue
- 4
- pages
- 1839 - 1847
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 12:16:07
- date last changed
- 2022-04-29 03:01:41
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M704576200}},
volume = {{283}},
year = {{2008}},
}