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Immune responses against oxidized LDL as possible targets for prevention of atherosclerosis in systemic lupus erythematosus

Yao Mattisson, Ingrid LU ; Rattik, Sara LU ; Björkbacka, Harry LU orcid ; Ljungcrantz, Irena LU ; Terrinoni, Manuela ; Lebens, Michael ; Holmgren, Jan ; Fredrikson, Gunilla Nordin LU ; Gullstrand, Birgitta LU and Bengtsson, Anders A. LU , et al. (2021) In Vascular Pharmacology 140.
Abstract

Patients suffering from systemic lupus erythematosus (SLE) are at increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. To investigate the possible role of oxidized LDL autoimmunity in the accelerated atherosclerosis associated with SLE we used a hypercholesterolemic SLE mouse model (B6.lpr.ApoE−/−... (More)

Patients suffering from systemic lupus erythematosus (SLE) are at increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. To investigate the possible role of oxidized LDL autoimmunity in the accelerated atherosclerosis associated with SLE we used a hypercholesterolemic SLE mouse model (B6.lpr.ApoE−/− mice). Promoting LDL tolerance through mucosal immunization with an apolipoprotein B-100 peptide p45 (amino acids 661–680) and cholera toxin B-subunit fusion protein increased regulatory T cells and B cells in mesenteric lymph nodes and reduced plaque development in the aorta by 33%. Treatment with the oxidized LDL-specific antibody Orticumab reduced aortic atherosclerosis by 43%, subvalvular plaque area by 50% and the macrophage content by 31%. The present study provides support for oxLDL as a possible target for prevention of cardiovascular complications in SLE.

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type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Autoimmunity, oxLDL, Systemic lupus erythematosus, Vaccine
in
Vascular Pharmacology
volume
140
article number
106863
publisher
Elsevier
external identifiers
  • pmid:33857652
  • scopus:85104113081
ISSN
1537-1891
DOI
10.1016/j.vph.2021.106863
language
English
LU publication?
yes
id
ae96e788-e0dd-4262-a505-f8eb15539d63
date added to LUP
2021-04-26 14:33:34
date last changed
2024-06-01 09:47:40
@article{ae96e788-e0dd-4262-a505-f8eb15539d63,
  abstract     = {{<p>Patients suffering from systemic lupus erythematosus (SLE) are at increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. To investigate the possible role of oxidized LDL autoimmunity in the accelerated atherosclerosis associated with SLE we used a hypercholesterolemic SLE mouse model (B6.lpr.ApoE<sup>−/−</sup> mice). Promoting LDL tolerance through mucosal immunization with an apolipoprotein B-100 peptide p45 (amino acids 661–680) and cholera toxin B-subunit fusion protein increased regulatory T cells and B cells in mesenteric lymph nodes and reduced plaque development in the aorta by 33%. Treatment with the oxidized LDL-specific antibody Orticumab reduced aortic atherosclerosis by 43%, subvalvular plaque area by 50% and the macrophage content by 31%. The present study provides support for oxLDL as a possible target for prevention of cardiovascular complications in SLE.</p>}},
  author       = {{Yao Mattisson, Ingrid and Rattik, Sara and Björkbacka, Harry and Ljungcrantz, Irena and Terrinoni, Manuela and Lebens, Michael and Holmgren, Jan and Fredrikson, Gunilla Nordin and Gullstrand, Birgitta and Bengtsson, Anders A. and Nilsson, Jan and Wigren, Maria}},
  issn         = {{1537-1891}},
  keywords     = {{Atherosclerosis; Autoimmunity; oxLDL; Systemic lupus erythematosus; Vaccine}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Elsevier}},
  series       = {{Vascular Pharmacology}},
  title        = {{Immune responses against oxidized LDL as possible targets for prevention of atherosclerosis in systemic lupus erythematosus}},
  url          = {{http://dx.doi.org/10.1016/j.vph.2021.106863}},
  doi          = {{10.1016/j.vph.2021.106863}},
  volume       = {{140}},
  year         = {{2021}},
}