Autoimmune responses against the apo B-100 LDL receptor-binding site protect against arterial accumulation of lipids in LDL receptor deficient mice.
(2007) In Autoimmunity 40(2). p.122-130- Abstract
- Background: Oxidation of LDL is associated with generation of autoantibodies against a large number of different aldehyde-modified peptide sequences in apo B-100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding region of apo B-100 could potentially affect both cholesterol metabolism and atherosclerosis. The aim of the present study was to determine physiological effects of induction of immune responses against the apo B-100 LDL receptor-binding site in mice deficient for the LDL receptor. Methods and results: Mice received three immunizations, beginning at 6 weeks of age, with aldehyde-modified or nonmodified peptides corresponding to the amino acid sequence of the LDL receptor-binding site. Analysis of antibody... (More)
- Background: Oxidation of LDL is associated with generation of autoantibodies against a large number of different aldehyde-modified peptide sequences in apo B-100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding region of apo B-100 could potentially affect both cholesterol metabolism and atherosclerosis. The aim of the present study was to determine physiological effects of induction of immune responses against the apo B-100 LDL receptor-binding site in mice deficient for the LDL receptor. Methods and results: Mice received three immunizations, beginning at 6 weeks of age, with aldehyde-modified or nonmodified peptides corresponding to the amino acid sequence of the LDL receptor-binding site. Analysis of antibody response by ELISA unexpectedly revealed high titers of pre-existing IgG against both native and aldehyde-modified binding site sequences in non-immunized mice. Immunization with aldehyde-modified binding site sequences resulted in an almost complete down-regulation of this autoimmune response. It was also associated with a rapid increase in lipid-rich plaques in the aorta and a substantial depletion of the lipid content of the liver, whereas plasma lipid and apo B values were similar in all groups. Conclusions: These observations demonstrate existence of an endogenous T cell-dependent autoimmune response against the LDL receptor-binding site in LDL receptor(-/-) mice and suggest that this may help to prevent accumulation of lipoprotein lipids in the artery wall, whereas immunization with the corresponding aldehyde modified sequence down-regulates this response and induces substantial atherosclerotic development. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/167409
- author
- Nordin Fredrikson, Gunilla LU ; Lindholm, Marie LU ; Ljungcrantz, Irena LU ; Söderberg, Ingrid LU ; Shah, Prediman K and Nilsson, Jan LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- apolipoprotein, autoantibodies, LDL-receptor, binding-site, atherosclerosis
- in
- Autoimmunity
- volume
- 40
- issue
- 2
- pages
- 122 - 130
- publisher
- Taylor & Francis
- external identifiers
-
- wos:000246108100006
- scopus:34250319739
- pmid:17453711
- ISSN
- 0891-6934
- DOI
- 10.1080/08916930601165107
- language
- English
- LU publication?
- yes
- id
- 07b5bf6d-5292-47cb-af52-6308869b9ad4 (old id 167409)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17453711&dopt=Abstract
- date added to LUP
- 2016-04-01 15:37:58
- date last changed
- 2022-02-27 07:57:40
@article{07b5bf6d-5292-47cb-af52-6308869b9ad4, abstract = {{Background: Oxidation of LDL is associated with generation of autoantibodies against a large number of different aldehyde-modified peptide sequences in apo B-100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding region of apo B-100 could potentially affect both cholesterol metabolism and atherosclerosis. The aim of the present study was to determine physiological effects of induction of immune responses against the apo B-100 LDL receptor-binding site in mice deficient for the LDL receptor. Methods and results: Mice received three immunizations, beginning at 6 weeks of age, with aldehyde-modified or nonmodified peptides corresponding to the amino acid sequence of the LDL receptor-binding site. Analysis of antibody response by ELISA unexpectedly revealed high titers of pre-existing IgG against both native and aldehyde-modified binding site sequences in non-immunized mice. Immunization with aldehyde-modified binding site sequences resulted in an almost complete down-regulation of this autoimmune response. It was also associated with a rapid increase in lipid-rich plaques in the aorta and a substantial depletion of the lipid content of the liver, whereas plasma lipid and apo B values were similar in all groups. Conclusions: These observations demonstrate existence of an endogenous T cell-dependent autoimmune response against the LDL receptor-binding site in LDL receptor(-/-) mice and suggest that this may help to prevent accumulation of lipoprotein lipids in the artery wall, whereas immunization with the corresponding aldehyde modified sequence down-regulates this response and induces substantial atherosclerotic development.}}, author = {{Nordin Fredrikson, Gunilla and Lindholm, Marie and Ljungcrantz, Irena and Söderberg, Ingrid and Shah, Prediman K and Nilsson, Jan}}, issn = {{0891-6934}}, keywords = {{apolipoprotein; autoantibodies; LDL-receptor; binding-site; atherosclerosis}}, language = {{eng}}, number = {{2}}, pages = {{122--130}}, publisher = {{Taylor & Francis}}, series = {{Autoimmunity}}, title = {{Autoimmune responses against the apo B-100 LDL receptor-binding site protect against arterial accumulation of lipids in LDL receptor deficient mice.}}, url = {{http://dx.doi.org/10.1080/08916930601165107}}, doi = {{10.1080/08916930601165107}}, volume = {{40}}, year = {{2007}}, }