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Jan Nilsson

Professor

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Medial Expression of TNF-α and TNF Receptors Precedes the Development of Atherosclerotic Lesions in Apolipoprotein E/LDL Receptor Double Knockout Mice

Author

  • Audrey Niemann-Jönsson
  • Ingrid Söderberg
  • Marie Lindholm
  • Stefan Jovinge
  • Jan Nilsson
  • Gunilla Nordin Fredrikson

Summary, in English

TNF-α is present in atherosclerotic lesions, activates endothelial adhesion molecule expression, stimulates the release of proinflammatory cytokines and matrix metalloproteinases and promotes smooth muscle cell proliferation and migration. Taken together these observations suggest that TNF-α may be functionally involved in early atherosclerosis development. To further evaluate this hypothesis we compared vascular TNF-α and TNF receptor expression in atherosclerosis-susceptible apoE-/-/LDL receptor-/- mice and control C57BL/6 mice. The aortas of 8 week old apoE-/-/LDLreceptor-/- mice displayed immunoreactivity for TNF-α as well as TNF p55 and p75 receptors (2.1 ± 1.6%, 5.6 ± 1.5% and 3.6 ± 1.3% of total media area, respectively), but did not have any detectable lesions. A marginal increase in TNF-α and TNF receptor immunoreactivity was observed at 12 weeks and atherosclerotic plaques were detected in 1 out of 5 animals. At 16 weeks TNF-α expression in the media was increased more than four-fold as compared with 8 week old mice, and atherosclerosis was widespread. TNF-α immunoreactivity was also observed in all plaques. In addition, at the same age a tendency towards increased TNF-α mRNA levels was detected in the double knockout mice compared to age-matched controls. A further increase in TNF-α and TNF receptor immunoreactivity as well as plaque size was observed at 20 weeks. With only a few exceptions, no TNF-α or TNF receptor immunoreactivity was detected in C57BL/6 control mice. These findings demonstrate that medial TNF-α and TNF receptor expression precedes lesion formation in apoE-/-/LDL receptor-/- mice.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis
  • Stem Cell Center

Publishing year

2007

Language

English

Pages

117-123

Publication/Series

International Journal of Biomedical Science

Volume

3

Issue

2

Document type

Journal article

Publisher

Master Publishing Group

Topic

  • Cardiac and Cardiovascular Systems
  • Cell and Molecular Biology

Keywords

  • TNF-α
  • TNF receptors
  • atherosclerosis
  • lipoproteins

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1550-9702