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Identification of the target for therapeutic recombinant anti-apoB-100 peptide antibodies in human atherosclerotic lesions.

Goncalves, Isabel LU ; Nitulescu, Mihaela LU ; Ares, Mikko LU ; Nordin Fredrikson, Gunilla LU ; Jansson, Bo; Li, Zhan-Chun and Nilsson, Jan LU (2009) In Atherosclerosis 205. p.96-100
Abstract
PURPOSE: Accumulation of oxidized LDL in the arterial wall is believed to play a key role in the development of atherosclerosis. Experimental studies have identified the presence of immune responses against epitopes in oxidized LDL that protects against atherosclerosis. We have produced human recombinant IgG against one of these epitopes (aldehyde-modified apoB-100 amino acids 661-680) and demonstrated that treatment with this human IgG1 2D03 antibody markedly reduces atherosclerosis in hypercholesterolemic mice. METHODS: In the present study, we screened a panel of 25 carotid plaques associated with clinical symptoms and 26 clinically silent plaques obtained at surgery for presence of the aldehyde-modified apoB-100 peptide defined by the... (More)
PURPOSE: Accumulation of oxidized LDL in the arterial wall is believed to play a key role in the development of atherosclerosis. Experimental studies have identified the presence of immune responses against epitopes in oxidized LDL that protects against atherosclerosis. We have produced human recombinant IgG against one of these epitopes (aldehyde-modified apoB-100 amino acids 661-680) and demonstrated that treatment with this human IgG1 2D03 antibody markedly reduces atherosclerosis in hypercholesterolemic mice. METHODS: In the present study, we screened a panel of 25 carotid plaques associated with clinical symptoms and 26 clinically silent plaques obtained at surgery for presence of the aldehyde-modified apoB-100 peptide defined by the 2D03 antibody and compared the expression of this epitope with other plaque constituents, plasma lipoproteins levels, plasma oxidized LDL and autoantibodies against apoB-100 peptides. RESULTS: We demonstrated that the epitope is commonly expressed in human atherosclerotic plaques and that plaques associated with clinical symptoms have an almost three-fold higher content of this epitope (8.6+/-4.9% versus 22.1+/-12.2% immunostaining of total plaque area, p<0.0005). There was also a significant association between 2D03 epitope staining and the plaque content of cholesterol esters (r=0.43, p<0.05), whereas there was no association with plasma oxidized LDL and autoantibodies against apoB-100 peptides. CONCLUSIONS: By demonstrating the presence of the 2D03 epitope in human atherosclerotic lesions our findings support the possibility that treatment with this antibody may have beneficial effects also in humans. Furthermore, they suggest the possibility to use these or other similar antibodies for diagnostic imaging of atherosclerotic plaques in humans. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Atherosclerosis
volume
205
pages
96 - 100
publisher
Elsevier
external identifiers
  • wos:000268115000015
  • pmid:19150065
  • scopus:67349120029
ISSN
1879-1484
DOI
10.1016/j.atherosclerosis.2008.11.020
language
English
LU publication?
yes
id
e71fbc5b-0e54-4255-877b-1a9851ccf644 (old id 1289611)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19150065?dopt=Abstract
date added to LUP
2009-02-04 11:17:56
date last changed
2017-01-01 07:38:48
@article{e71fbc5b-0e54-4255-877b-1a9851ccf644,
  abstract     = {PURPOSE: Accumulation of oxidized LDL in the arterial wall is believed to play a key role in the development of atherosclerosis. Experimental studies have identified the presence of immune responses against epitopes in oxidized LDL that protects against atherosclerosis. We have produced human recombinant IgG against one of these epitopes (aldehyde-modified apoB-100 amino acids 661-680) and demonstrated that treatment with this human IgG1 2D03 antibody markedly reduces atherosclerosis in hypercholesterolemic mice. METHODS: In the present study, we screened a panel of 25 carotid plaques associated with clinical symptoms and 26 clinically silent plaques obtained at surgery for presence of the aldehyde-modified apoB-100 peptide defined by the 2D03 antibody and compared the expression of this epitope with other plaque constituents, plasma lipoproteins levels, plasma oxidized LDL and autoantibodies against apoB-100 peptides. RESULTS: We demonstrated that the epitope is commonly expressed in human atherosclerotic plaques and that plaques associated with clinical symptoms have an almost three-fold higher content of this epitope (8.6+/-4.9% versus 22.1+/-12.2% immunostaining of total plaque area, p&lt;0.0005). There was also a significant association between 2D03 epitope staining and the plaque content of cholesterol esters (r=0.43, p&lt;0.05), whereas there was no association with plasma oxidized LDL and autoantibodies against apoB-100 peptides. CONCLUSIONS: By demonstrating the presence of the 2D03 epitope in human atherosclerotic lesions our findings support the possibility that treatment with this antibody may have beneficial effects also in humans. Furthermore, they suggest the possibility to use these or other similar antibodies for diagnostic imaging of atherosclerotic plaques in humans.},
  author       = {Goncalves, Isabel and Nitulescu, Mihaela and Ares, Mikko and Nordin Fredrikson, Gunilla and Jansson, Bo and Li, Zhan-Chun and Nilsson, Jan},
  issn         = {1879-1484},
  language     = {eng},
  pages        = {96--100},
  publisher    = {Elsevier},
  series       = {Atherosclerosis},
  title        = {Identification of the target for therapeutic recombinant anti-apoB-100 peptide antibodies in human atherosclerotic lesions.},
  url          = {http://dx.doi.org/10.1016/j.atherosclerosis.2008.11.020},
  volume       = {205},
  year         = {2009},
}