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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

Niemann-Jönsson, Audrey; Söderberg, Ingrid LU ; Lindholm, Marie LU ; Jovinge, Stefan LU ; Nilsson, Jan LU and Nordin Fredrikson, Gunilla LU (2007) In International Journal of Biomedical Science 3(2). p.117-123
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
TNF-α, TNF receptors, atherosclerosis, lipoproteins
in
International Journal of Biomedical Science
volume
3
issue
2
pages
117 - 123
publisher
Master Publishing Group
ISSN
1550-9702
language
English
LU publication?
yes
id
8763dfcc-58eb-4264-a1af-3753281febee (old id 1140250)
alternative location
http://www.ijbs.org/User/All-by-date.aspx
date added to LUP
2008-08-21 15:00:51
date last changed
2016-04-15 19:25:17
@article{8763dfcc-58eb-4264-a1af-3753281febee,
  abstract     = {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.},
  author       = {Niemann-Jönsson, Audrey and Söderberg, Ingrid and Lindholm, Marie and Jovinge, Stefan and Nilsson, Jan and Nordin Fredrikson, Gunilla},
  issn         = {1550-9702},
  keyword      = {TNF-α,TNF receptors,atherosclerosis,lipoproteins},
  language     = {eng},
  number       = {2},
  pages        = {117--123},
  publisher    = {Master Publishing Group},
  series       = {International Journal of Biomedical Science},
  title        = {Medial Expression of TNF-α and TNF Receptors Precedes the Development of Atherosclerotic Lesions in Apolipoprotein E/LDL Receptor Double Knockout Mice},
  volume       = {3},
  year         = {2007},
}