Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice
Author
Summary, in English
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.
Department/s
Publishing year
2008
Language
English
Pages
1839-1847
Publication/Series
Journal of Biological Chemistry
Volume
283
Issue
4
Document type
Journal article
Publisher
American Society for Biochemistry and Molecular Biology
Topic
- Medicinal Chemistry
Status
Published
Research group
- Clinical Chemistry, Malmö
ISBN/ISSN/Other
- ISSN: 1083-351X