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The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice

Pedersen, Tanja X.; Binder, Christoph J.; Nordin Fredrikson, Gunilla LU ; Nilsson, Jan LU ; Bro, Susanne and Nielsen, Lars B. (2010) In Nephrology Dialysis Transplantation 25(8). p.2486-2491
Abstract
Background. Uraemia increases oxidative stress, plasma titres of antibodies recognizing oxidized low-density lipoprotein (oxLDL) and development of atherosclerosis. Immunization with oxLDL prevents classical, non-uraemic atherosclerosis. We have investigated whether immunization with oxLDL might also prevent uraemia-induced atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. Methods. ApoE-/- mice were immunized with either native LDL (n = 25), Cu2+-oxidized LDL (n = 25), PBS (n = 25), the apolipoprotein B-derived peptide P45 (apoB-peptide P45) conjugated to bovine serum albumin (BSA) (n = 25) or BSA (n = 25) prior to induction of uraemia by 5/6 nephrectomy (NX). Results. Immunization with oxLDL increased plasma titres of... (More)
Background. Uraemia increases oxidative stress, plasma titres of antibodies recognizing oxidized low-density lipoprotein (oxLDL) and development of atherosclerosis. Immunization with oxLDL prevents classical, non-uraemic atherosclerosis. We have investigated whether immunization with oxLDL might also prevent uraemia-induced atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. Methods. ApoE-/- mice were immunized with either native LDL (n = 25), Cu2+-oxidized LDL (n = 25), PBS (n = 25), the apolipoprotein B-derived peptide P45 (apoB-peptide P45) conjugated to bovine serum albumin (BSA) (n = 25) or BSA (n = 25) prior to induction of uraemia by 5/6 nephrectomy (NX). Results. Immunization with oxLDL increased plasma titres of immunoglobulin G (IgG) recognizing Cu2+-oxLDL and malondialdehyde-modified LDL (MDA-LDL). However, 5/6 NX induced a marked increase in plasma concentrations of anti-oxLDL antibodies as well as pro-atherogenic cytokines [interleukin (IL)-2 (IL-2), IL-4, IL-6 and IL-12)] in native mouse LDL (nLDL)-, oxLDL- and PBS-immunized mice. Even though nLDL- and oxLDL-immunized mice displayed higher anti-MDA-LDL IgG titres than the PBS group, aortic atherosclerosis lesion size was not affected by immunization. Immunization with the apoB-peptide P45, which consistently reduces classical atherosclerosis in non-uraemic mice, also did not reduce lesion size in uraemic apoE-/- mice. Conclusion. The results suggest that the pro-inflammatory and pro-atherogenic effect of uraemia overrules the anti-atherogenic potential of oxLDL immunization in apoE-/- mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, oxLDL immunization, uraemia
in
Nephrology Dialysis Transplantation
volume
25
issue
8
pages
2486 - 2491
publisher
Oxford University Press
external identifiers
  • wos:000281483300017
  • scopus:77954805100
ISSN
1460-2385
DOI
10.1093/ndt/gfq059
language
English
LU publication?
yes
id
8f30d81d-62e2-494d-93c1-2adb003ded16 (old id 1672295)
date added to LUP
2010-09-23 14:47:47
date last changed
2018-05-29 11:21:48
@article{8f30d81d-62e2-494d-93c1-2adb003ded16,
  abstract     = {Background. Uraemia increases oxidative stress, plasma titres of antibodies recognizing oxidized low-density lipoprotein (oxLDL) and development of atherosclerosis. Immunization with oxLDL prevents classical, non-uraemic atherosclerosis. We have investigated whether immunization with oxLDL might also prevent uraemia-induced atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. Methods. ApoE-/- mice were immunized with either native LDL (n = 25), Cu2+-oxidized LDL (n = 25), PBS (n = 25), the apolipoprotein B-derived peptide P45 (apoB-peptide P45) conjugated to bovine serum albumin (BSA) (n = 25) or BSA (n = 25) prior to induction of uraemia by 5/6 nephrectomy (NX). Results. Immunization with oxLDL increased plasma titres of immunoglobulin G (IgG) recognizing Cu2+-oxLDL and malondialdehyde-modified LDL (MDA-LDL). However, 5/6 NX induced a marked increase in plasma concentrations of anti-oxLDL antibodies as well as pro-atherogenic cytokines [interleukin (IL)-2 (IL-2), IL-4, IL-6 and IL-12)] in native mouse LDL (nLDL)-, oxLDL- and PBS-immunized mice. Even though nLDL- and oxLDL-immunized mice displayed higher anti-MDA-LDL IgG titres than the PBS group, aortic atherosclerosis lesion size was not affected by immunization. Immunization with the apoB-peptide P45, which consistently reduces classical atherosclerosis in non-uraemic mice, also did not reduce lesion size in uraemic apoE-/- mice. Conclusion. The results suggest that the pro-inflammatory and pro-atherogenic effect of uraemia overrules the anti-atherogenic potential of oxLDL immunization in apoE-/- mice.},
  author       = {Pedersen, Tanja X. and Binder, Christoph J. and Nordin Fredrikson, Gunilla and Nilsson, Jan and Bro, Susanne and Nielsen, Lars B.},
  issn         = {1460-2385},
  keyword      = {atherosclerosis,oxLDL immunization,uraemia},
  language     = {eng},
  number       = {8},
  pages        = {2486--2491},
  publisher    = {Oxford University Press},
  series       = {Nephrology Dialysis Transplantation},
  title        = {The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice},
  url          = {http://dx.doi.org/10.1093/ndt/gfq059},
  volume       = {25},
  year         = {2010},
}