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

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Author

  • Tanja X. Pedersen
  • Christoph J. Binder
  • Gunilla Nordin Fredrikson
  • Jan Nilsson
  • Susanne Bro
  • Lars B. Nielsen

Summary, in English

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.

Publishing year

2010

Language

English

Pages

2486-2491

Publication/Series

Nephrology Dialysis Transplantation

Volume

25

Issue

8

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Urology and Nephrology

Keywords

  • atherosclerosis
  • oxLDL immunization
  • uraemia

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1460-2385