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

Author:
  • Isabel Goncalves
  • Mihaela Nitulescu
  • Mikko Ares
  • Gunilla Nordin Fredrikson
  • Bo Jansson
  • Zhan-Chun Li
  • Jan Nilsson
Publishing year: 2009
Language: English
Pages: 96-100
Publication/Series: Atherosclerosis
Volume: 205
Document type: Journal article
Publisher: Elsevier

Abstract english

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.

Keywords

  • Cardiac and Cardiovascular Systems

Other

Published
  • Cardiovascular Research - Immunity and Athersosclerosis
  • ISSN: 1879-1484
E-mail: mihaela [dot] nitulescu [at] med [dot] lu [dot] se

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