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Autoimmune responses against the apo B-100 LDL receptor-binding site protect against arterial accumulation of lipids in LDL receptor deficient mice.

Author:
  • Gunilla Nordin Fredrikson
  • Marie Lindholm
  • Irena Ljungcrantz
  • Ingrid Söderberg
  • Prediman K Shah
  • Jan Nilsson
Publishing year: 2007
Language: English
Pages: 122-130
Publication/Series: Autoimmunity
Volume: 40
Issue: 2
Document type: Journal article
Publisher: Taylor & Francis

Abstract english

Background: Oxidation of LDL is associated with generation of autoantibodies against a large number of different aldehyde-modified peptide sequences in apo B-100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding region of apo B-100 could potentially affect both cholesterol metabolism and atherosclerosis. The aim of the present study was to determine physiological effects of induction of immune responses against the apo B-100 LDL receptor-binding site in mice deficient for the LDL receptor. Methods and results: Mice received three immunizations, beginning at 6 weeks of age, with aldehyde-modified or nonmodified peptides corresponding to the amino acid sequence of the LDL receptor-binding site. Analysis of antibody response by ELISA unexpectedly revealed high titers of pre-existing IgG against both native and aldehyde-modified binding site sequences in non-immunized mice. Immunization with aldehyde-modified binding site sequences resulted in an almost complete down-regulation of this autoimmune response. It was also associated with a rapid increase in lipid-rich plaques in the aorta and a substantial depletion of the lipid content of the liver, whereas plasma lipid and apo B values were similar in all groups. Conclusions: These observations demonstrate existence of an endogenous T cell-dependent autoimmune response against the LDL receptor-binding site in LDL receptor(-/-) mice and suggest that this may help to prevent accumulation of lipoprotein lipids in the artery wall, whereas immunization with the corresponding aldehyde modified sequence down-regulates this response and induces substantial atherosclerotic development.

Keywords

  • Rheumatology and Autoimmunity
  • apolipoprotein
  • autoantibodies
  • LDL-receptor
  • binding-site
  • atherosclerosis

Other

Published
  • Cardiovascular Research - Immunity and Athersosclerosis
  • ISSN: 0891-6934
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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