Antibodies against apoB100 peptide 210 inhibit atherosclerosis in apoE-/- mice
Dunér, Pontus LU ; Mattisson, Ingrid Yao LU ; Fogelstrand, Per ; Glise, Lars ; Ruiz, Stacey ; Farina, Christopher ; Borén, Jan ; Nilsson, Jan LU and Bengtsson, Eva LU
(2021)
In Scientific Reports
11(1).
- Abstract
Atherosclerotic plaques are characterized by an accumulation and subsequent oxidation of LDL, resulting in adaptive immune responses against formed or exposed neoepitopes of the LDL particle. Autoantibodies against native p210, the 3136–3155 amino acid sequence of the LDL protein apolipoprotein B-100 (apoB100) are common in humans and have been associated with less severe atherosclerosis and decreased risk for cardiovascular events in clinical studies. However, whether apoB100 native p210 autoantibodies play a functional role in atherosclerosis is not known. In the present study we immunized apoE-/- mice with p210-PADRE peptide to induce an antibody response against native p210. We also injected mice with murine monoclonal... (More)
Atherosclerotic plaques are characterized by an accumulation and subsequent oxidation of LDL, resulting in adaptive immune responses against formed or exposed neoepitopes of the LDL particle. Autoantibodies against native p210, the 3136–3155 amino acid sequence of the LDL protein apolipoprotein B-100 (apoB100) are common in humans and have been associated with less severe atherosclerosis and decreased risk for cardiovascular events in clinical studies. However, whether apoB100 native p210 autoantibodies play a functional role in atherosclerosis is not known. In the present study we immunized apoE-/- mice with p210-PADRE peptide to induce an antibody response against native p210. We also injected mice with murine monoclonal IgG against native p210. Control groups were immunized with PADRE peptide alone or with control murine monoclonal IgG. Immunization with p210-PADRE induced an IgG1 antibody response against p210 that was associated with reduced atherosclerotic plaque formation in the aorta and reduced MDA-LDL content in the lesions. Treatment with monoclonal p210 IgG produced a similar reduction in atherosclerosis as immunization with p210-PADRE. Our findings support an atheroprotective role of antibodies against the apoB100 native p210 and suggest that vaccines that induce the expression of native p210 IgG represent a potential therapeutic strategy for lowering cardiovascular risk.
(Less)
- author
- Dunér, Pontus
LU
; Mattisson, Ingrid Yao
LU
; Fogelstrand, Per
; Glise, Lars
; Ruiz, Stacey
; Farina, Christopher
; Borén, Jan
; Nilsson, Jan
LU
and Bengtsson, Eva
LU
- organization
- publishing date
- 2021-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 11
- issue
- 1
- article number
- 9022
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85105087780
- pmid:33907226
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-021-88430-1
- language
- English
- LU publication?
- yes
- id
- 6687b5bb-d91d-48b5-9774-bba0460df92f
- date added to LUP
- 2021-05-18 15:38:58
- date last changed
- 2024-07-13 13:41:57
@article{6687b5bb-d91d-48b5-9774-bba0460df92f,
abstract = {{<p>Atherosclerotic plaques are characterized by an accumulation and subsequent oxidation of LDL, resulting in adaptive immune responses against formed or exposed neoepitopes of the LDL particle. Autoantibodies against native p210, the 3136–3155 amino acid sequence of the LDL protein apolipoprotein B-100 (apoB100) are common in humans and have been associated with less severe atherosclerosis and decreased risk for cardiovascular events in clinical studies. However, whether apoB100 native p210 autoantibodies play a functional role in atherosclerosis is not known. In the present study we immunized apoE<sup>-/-</sup> mice with p210-PADRE peptide to induce an antibody response against native p210. We also injected mice with murine monoclonal IgG against native p210. Control groups were immunized with PADRE peptide alone or with control murine monoclonal IgG. Immunization with p210-PADRE induced an IgG1 antibody response against p210 that was associated with reduced atherosclerotic plaque formation in the aorta and reduced MDA-LDL content in the lesions. Treatment with monoclonal p210 IgG produced a similar reduction in atherosclerosis as immunization with p210-PADRE. Our findings support an atheroprotective role of antibodies against the apoB100 native p210 and suggest that vaccines that induce the expression of native p210 IgG represent a potential therapeutic strategy for lowering cardiovascular risk.</p>}},
author = {{Dunér, Pontus and Mattisson, Ingrid Yao and Fogelstrand, Per and Glise, Lars and Ruiz, Stacey and Farina, Christopher and Borén, Jan and Nilsson, Jan and Bengtsson, Eva}},
issn = {{2045-2322}},
language = {{eng}},
month = {{12}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Antibodies against apoB100 peptide 210 inhibit atherosclerosis in apoE<sup>-/-</sup> mice}},
url = {{http://dx.doi.org/10.1038/s41598-021-88430-1}},
doi = {{10.1038/s41598-021-88430-1}},
volume = {{11}},
year = {{2021}},
}