The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1672295
- author
- Pedersen, Tanja X. ; Binder, Christoph J. ; Nordin Fredrikson, Gunilla LU ; Nilsson, Jan LU ; Bro, Susanne and Nielsen, Lars B.
- organization
- publishing date
- 2010
- 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
- pmid:20164045
- 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
- 2016-04-01 13:32:51
- date last changed
- 2022-01-27 19:47:26
@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}}, keywords = {{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}}, doi = {{10.1093/ndt/gfq059}}, volume = {{25}}, year = {{2010}}, }