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Daniel Engelbertsen

Assistant researcher

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Activation of immune responses against the basement membrane component collagen type IV does not affect the development of atherosclerosis in ApoE-deficient mice

Author

  • J. Vallejo
  • P. Dunér
  • F. To
  • D. Engelbertsen
  • I. Gonçalves
  • J. Nilsson
  • E. Bengtsson

Summary, in English


Oxidation of low-density lipoprotein (LDL) in the arterial extracellular matrix results in malondialdehyde (MDA)-modifications of surrounding matrix proteins. We have recently demonstrated an association between high levels of autoantibodies against MDA-modified collagen type IV and risk for development of myocardial infarction. Collagen type IV is an important component of the endothelial basement membrane and influences smooth muscle cell function. We hypothesized that immune responses against collagen type IV could contribute to vascular injury affecting the development of atherosclerosis. To investigate this possibility, we induced an antibody-response against collagen type IV in apolipoprotein E (Apo E)-deficient mice. Female ApoE
−/−
mice on C57BL/6 background were immunized with α1α2 type IV collagen chain peptides linked to the immune-enhancer PADRE, PADRE alone or PBS at 12 weeks of age with three subsequent booster injections before the mice were killed at 23 weeks of age. Immunization of PADRE alone induced autoantibodies against PADRE, increased IL-4 secretion from splenocytes and reduced SMC content in the subvalvular plaques. Immunization with peptides of α1α2 type IV collagen chains induced a strong IgG1antibody response against collagen type IV peptides without affecting the distribution of T cell populations, plasma cytokine or lipid levels. There were no differences in atherosclerotic plaque development between collagen α1α2(IV)-PADRE immunized mice and control mice. Our findings demonstrate that the presence of antibodies against the basement membrane component collagen type IV does not affect atherosclerosis development in ApoE
−/−
mice. This suggests that the association between autoantibodies against collagen type IV and risk for myocardial infarction found in humans does not reflect a pathogenic role of these autoantibodies.

Department/s

  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • Cardiovascular Research - Translational Studies
  • Cardiovascular Research - Immunity and Atherosclerosis
  • EpiHealth: Epidemiology for Health

Publishing year

2019-04-12

Language

English

Publication/Series

Scientific Reports

Volume

9

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Rheumatology and Autoimmunity

Status

Published

Research group

  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • Cardiovascular Research - Translational Studies
  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 2045-2322