Advanced

Recombinant human antibodies against aldehyde-modified apolipoprotein B-100 peptide sequences inhibit atherosclerosis

Schiopu, Alexandru LU ; Bengtsson, J; Söderberg, Ingrid LU ; Janciauskiene, Sabina LU ; Lindgren, Stefan LU ; Ares, Mikko LU ; Shah, PK; Carlsson, R; Nilsson, Jan LU and Nordin Fredrikson, Gunilla LU (2004) In Circulation 110(14). p.2047-2052
Abstract
Background-Accumulation and oxidation of LDL are believed to be important initiating factors in atherosclerosis. Oxidized LDL is recognized by the immune system, and animal studies have suggested that these immune responses have a protective effect against atherosclerosis. Aldehyde-modified peptide sequences in apolipoprotein B-100 (apoB-100) are major targets for these immune responses. Methods and Results-Human IgG1 antibodies against 2 malondialdehyde (MDA)-modified apoB-100 peptide sequences were produced through screening of a single-chain antibody-fragment library and subsequent cloning into a pcDNA3 vector. Three weekly doses of these antibodies were injected into male apoE(-/-) mice. Phosphate-buffered saline and human IgG1... (More)
Background-Accumulation and oxidation of LDL are believed to be important initiating factors in atherosclerosis. Oxidized LDL is recognized by the immune system, and animal studies have suggested that these immune responses have a protective effect against atherosclerosis. Aldehyde-modified peptide sequences in apolipoprotein B-100 (apoB-100) are major targets for these immune responses. Methods and Results-Human IgG1 antibodies against 2 malondialdehyde (MDA)-modified apoB-100 peptide sequences were produced through screening of a single-chain antibody-fragment library and subsequent cloning into a pcDNA3 vector. Three weekly doses of these antibodies were injected into male apoE(-/-) mice. Phosphate-buffered saline and human IgG1 antibodies against fluorescein isothiocyanate were used as controls. One of the IgG1 antibodies significantly and dose-dependently reduced the extent of atherosclerosis as well as the plaque content of oxidized LDL epitopes and macrophages. In cell culture studies, human monocytes were incubated with native LDL or oxidized LDL, in the presence of antibodies. The same antibody induced an increase in monocyte binding and uptake of oxidized LDL. Conclusions-These findings suggest that antibodies are important mediators of atheroprotective immune responses directed to oxidized LDL. Thus, passive immunization against MDA-modified apoB-100 peptide sequences may represent a novel therapeutic approach for prevention and treatment of cardiovascular disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apolipoproteins, immune system, antibodies, atherosclerosis, plaque
in
Circulation
volume
110
issue
14
pages
2047 - 2052
publisher
Lippincott Williams and Wilkins
external identifiers
  • pmid:15451805
  • wos:000224262100027
  • scopus:20844432027
ISSN
1524-4539
DOI
10.1161/01.CIR.0000143162.56057.B5
language
English
LU publication?
yes
id
d20c7339-7cba-427f-9e58-232ff79e85a9 (old id 266548)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15451805&dopt=Abstract
date added to LUP
2007-10-31 13:11:15
date last changed
2017-11-05 04:24:29
@article{d20c7339-7cba-427f-9e58-232ff79e85a9,
  abstract     = {Background-Accumulation and oxidation of LDL are believed to be important initiating factors in atherosclerosis. Oxidized LDL is recognized by the immune system, and animal studies have suggested that these immune responses have a protective effect against atherosclerosis. Aldehyde-modified peptide sequences in apolipoprotein B-100 (apoB-100) are major targets for these immune responses. Methods and Results-Human IgG1 antibodies against 2 malondialdehyde (MDA)-modified apoB-100 peptide sequences were produced through screening of a single-chain antibody-fragment library and subsequent cloning into a pcDNA3 vector. Three weekly doses of these antibodies were injected into male apoE(-/-) mice. Phosphate-buffered saline and human IgG1 antibodies against fluorescein isothiocyanate were used as controls. One of the IgG1 antibodies significantly and dose-dependently reduced the extent of atherosclerosis as well as the plaque content of oxidized LDL epitopes and macrophages. In cell culture studies, human monocytes were incubated with native LDL or oxidized LDL, in the presence of antibodies. The same antibody induced an increase in monocyte binding and uptake of oxidized LDL. Conclusions-These findings suggest that antibodies are important mediators of atheroprotective immune responses directed to oxidized LDL. Thus, passive immunization against MDA-modified apoB-100 peptide sequences may represent a novel therapeutic approach for prevention and treatment of cardiovascular disease.},
  author       = {Schiopu, Alexandru and Bengtsson, J and Söderberg, Ingrid and Janciauskiene, Sabina and Lindgren, Stefan and Ares, Mikko and Shah, PK and Carlsson, R and Nilsson, Jan and Nordin Fredrikson, Gunilla},
  issn         = {1524-4539},
  keyword      = {apolipoproteins,immune system,antibodies,atherosclerosis,plaque},
  language     = {eng},
  number       = {14},
  pages        = {2047--2052},
  publisher    = {Lippincott Williams and Wilkins},
  series       = {Circulation},
  title        = {Recombinant human antibodies against aldehyde-modified apolipoprotein B-100 peptide sequences inhibit atherosclerosis},
  url          = {http://dx.doi.org/10.1161/01.CIR.0000143162.56057.B5},
  volume       = {110},
  year         = {2004},
}