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Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL

Elsoe, Sara; Ahnstrom, Josefin; Christoffersen, Christina; Hoofnagle, Andrew N.; Plomgaard, Peter; Heinecke, Jay W.; Binder, Christoph J.; Björkbacka, Harry LU ; Dahlbäck, Björn LU and Nielsen, Lars B. (2012) In Atherosclerosis 221(1). p.91-97
Abstract
Objective: Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL. Methods and results: HDL was isolated from wild type mice, apoM-deficient mice, and two lines of apoM-Tg mice with similar to 2-fold and similar to 10-fold increased plasma apoM, respectively. Increasing amounts of... (More)
Objective: Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL. Methods and results: HDL was isolated from wild type mice, apoM-deficient mice, and two lines of apoM-Tg mice with similar to 2-fold and similar to 10-fold increased plasma apoM, respectively. Increasing amounts of HDL-associated apoM were associated with an increase in the resistance of HDL to oxidation with Cu2+ or 2,2'-azobis 2-methyl-propanimidamide, dihydrochloride (AAPH) and to an increased ability of HDL to protect human LDL against oxidation. Oxidized phospholipids, but not native phospholipids, quenched the intrinsic fluorescence of recombinant human apoM and the quenching could be competed with myristic acid suggesting selective binding of oxidized phospholipid in the lipocalin-binding pocket of apoM. Conclusions: The results suggest that apoM can bind oxidized phospholipids and that it increases the antioxidant effect of HDL. This new mechanism may explain at least part of the antiatherogenic potential of apoM. (C) 2011 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apolipoprotein M, HDL, Antioxidant, Oxidized phospholipids, Atherosclerosis
in
Atherosclerosis
volume
221
issue
1
pages
91 - 97
publisher
Elsevier
external identifiers
  • wos:000300629500013
  • scopus:84857029613
ISSN
1879-1484
DOI
10.1016/j.atherosclerosis.2011.11.031
language
English
LU publication?
yes
id
7cdd6959-527b-4b52-bd81-e0b39cd78662 (old id 2390892)
date added to LUP
2012-04-02 09:25:44
date last changed
2017-11-19 03:17:09
@article{7cdd6959-527b-4b52-bd81-e0b39cd78662,
  abstract     = {Objective: Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL. Methods and results: HDL was isolated from wild type mice, apoM-deficient mice, and two lines of apoM-Tg mice with similar to 2-fold and similar to 10-fold increased plasma apoM, respectively. Increasing amounts of HDL-associated apoM were associated with an increase in the resistance of HDL to oxidation with Cu2+ or 2,2'-azobis 2-methyl-propanimidamide, dihydrochloride (AAPH) and to an increased ability of HDL to protect human LDL against oxidation. Oxidized phospholipids, but not native phospholipids, quenched the intrinsic fluorescence of recombinant human apoM and the quenching could be competed with myristic acid suggesting selective binding of oxidized phospholipid in the lipocalin-binding pocket of apoM. Conclusions: The results suggest that apoM can bind oxidized phospholipids and that it increases the antioxidant effect of HDL. This new mechanism may explain at least part of the antiatherogenic potential of apoM. (C) 2011 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Elsoe, Sara and Ahnstrom, Josefin and Christoffersen, Christina and Hoofnagle, Andrew N. and Plomgaard, Peter and Heinecke, Jay W. and Binder, Christoph J. and Björkbacka, Harry and Dahlbäck, Björn and Nielsen, Lars B.},
  issn         = {1879-1484},
  keyword      = {Apolipoprotein M,HDL,Antioxidant,Oxidized phospholipids,Atherosclerosis},
  language     = {eng},
  number       = {1},
  pages        = {91--97},
  publisher    = {Elsevier},
  series       = {Atherosclerosis},
  title        = {Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL},
  url          = {http://dx.doi.org/10.1016/j.atherosclerosis.2011.11.031},
  volume       = {221},
  year         = {2012},
}