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Inhibition of injury-induced arterial remodelling and carotid atherosclerosis by recombinant human antibodies against aldehyde-modified apoB-100.

Ström, Åsa LU ; Nordin Fredrikson, Gunilla LU ; Schiopu, Alexandru LU ; Ljungcrantz, Irena LU ; Söderberg, Ingrid LU ; Jansson, Bo ; Carlsson, Roland ; Hultgårdh, Anna LU and Nilsson, Jan LU (2007) In Atherosclerosis 190(2). p.298-305
Abstract
Objective: The immune system plays an important regulatory role in the development of atherosclerotic plaques and neointima formation following various types of angioplasty. In the present study we investigated the effect of antibodies against aldehyde-modified apolipoprotein B-100 (apoB-100), a component of oxidized LDL, on atherosclerosis and response to arterial injury in mice. Methods: The ability of a high affinity human recombinant antibody (21303), specific for malondialdehyde-modified apoB-100, to influence formation of atherosclerosis as well as remodelling and neointima formation after a collar-induced injury of the carotid artery was studied in LDL receptor(-/-) mice over-expressing human apoB-100. Results: The antibody... (More)
Objective: The immune system plays an important regulatory role in the development of atherosclerotic plaques and neointima formation following various types of angioplasty. In the present study we investigated the effect of antibodies against aldehyde-modified apolipoprotein B-100 (apoB-100), a component of oxidized LDL, on atherosclerosis and response to arterial injury in mice. Methods: The ability of a high affinity human recombinant antibody (21303), specific for malondialdehyde-modified apoB-100, to influence formation of atherosclerosis as well as remodelling and neointima formation after a collar-induced injury of the carotid artery was studied in LDL receptor(-/-) mice over-expressing human apoB-100. Results: The antibody recognized epitopes present in mouse plasma and reduced the plasma level of oxidized LDL by 34%. Antibody treatment inhibited injury-induced restrictive vascular remodelling but did not influence the size of the neointima. Atherosclerosis in the uninjured contra lateral carotid artery was determined by computerized image analysis and the mean plaque area in animals given control IgG1 was 7608 +/- 10,336 mu m(2). In contrast, essentially no plaques were present in animals treated with the 2DO3 antibody (397 +/- 235 mu m(2), P < 0.0 1 versus control IgG 1). Conclusions: Treatment with antibodies against aldehyde-modified apoB-100 dramatically reduces atherosclerosis and inhibits restrictive vascular remodelling in mice expressing human apoB-100. (c) 2006 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, oxidized LDL, apolipoprotein B-100, antibodies, vascular injury
in
Atherosclerosis
volume
190
issue
2
pages
298 - 305
publisher
Elsevier
external identifiers
  • wos:000244173000008
  • scopus:33846064690
ISSN
1879-1484
DOI
10.1016/j.atherosclerosis.2006.03.032
language
English
LU publication?
yes
id
9f0856d1-e353-4721-9f74-e9680d1ea329 (old id 157000)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16677655&dopt=Abstract
date added to LUP
2016-04-01 12:12:24
date last changed
2022-01-27 00:21:56
@article{9f0856d1-e353-4721-9f74-e9680d1ea329,
  abstract     = {{Objective: The immune system plays an important regulatory role in the development of atherosclerotic plaques and neointima formation following various types of angioplasty. In the present study we investigated the effect of antibodies against aldehyde-modified apolipoprotein B-100 (apoB-100), a component of oxidized LDL, on atherosclerosis and response to arterial injury in mice. Methods: The ability of a high affinity human recombinant antibody (21303), specific for malondialdehyde-modified apoB-100, to influence formation of atherosclerosis as well as remodelling and neointima formation after a collar-induced injury of the carotid artery was studied in LDL receptor(-/-) mice over-expressing human apoB-100. Results: The antibody recognized epitopes present in mouse plasma and reduced the plasma level of oxidized LDL by 34%. Antibody treatment inhibited injury-induced restrictive vascular remodelling but did not influence the size of the neointima. Atherosclerosis in the uninjured contra lateral carotid artery was determined by computerized image analysis and the mean plaque area in animals given control IgG1 was 7608 +/- 10,336 mu m(2). In contrast, essentially no plaques were present in animals treated with the 2DO3 antibody (397 +/- 235 mu m(2), P &lt; 0.0 1 versus control IgG 1). Conclusions: Treatment with antibodies against aldehyde-modified apoB-100 dramatically reduces atherosclerosis and inhibits restrictive vascular remodelling in mice expressing human apoB-100. (c) 2006 Elsevier Ireland Ltd. All rights reserved.}},
  author       = {{Ström, Åsa and Nordin Fredrikson, Gunilla and Schiopu, Alexandru and Ljungcrantz, Irena and Söderberg, Ingrid and Jansson, Bo and Carlsson, Roland and Hultgårdh, Anna and Nilsson, Jan}},
  issn         = {{1879-1484}},
  keywords     = {{atherosclerosis; oxidized LDL; apolipoprotein B-100; antibodies; vascular injury}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{298--305}},
  publisher    = {{Elsevier}},
  series       = {{Atherosclerosis}},
  title        = {{Inhibition of injury-induced arterial remodelling and carotid atherosclerosis by recombinant human antibodies against aldehyde-modified apoB-100.}},
  url          = {{http://dx.doi.org/10.1016/j.atherosclerosis.2006.03.032}},
  doi          = {{10.1016/j.atherosclerosis.2006.03.032}},
  volume       = {{190}},
  year         = {{2007}},
}