Advanced

Inhibition of Tumor Necrosis Factor-{alpha} Reduces Atherosclerosis in Apolipoprotein E Knockout Mice.

Brånén, Lena LU ; Hovgaard, Lars; Nitulescu, Mihaela LU ; Bengtsson, Eva LU ; Nilsson, Jan LU and Jovinge, Stefan LU (2004) In Arteriosclerosis, Thrombosis and Vascular Biology 24(11). p.2137-2142
Abstract
Objective - Inflammation plays an important role in atherosclerosis. One of the most potent pro-inflammatory cytokines is tumor necrosis factor-alpha (TNF-alpha), a cytokine identified to have a pathogenic role in chronic inflammatory diseases such as rheumatoid arthritis ( RA). The aim of the study was to evaluate the importance of TNF-alpha in atherogenesis. Methods and Results - Mice deficient in both apolipoprotein E (apoE) and TNF-alpha were compared regarding their atherosclerotic burden. Mice were fed a Western-style diet (WD) or normal chow. Mice deficient in both apoE and TNF-alpha exhibited a 50% ( P = 0.035) reduction of relative lesion size after 10 weeks of WD. Bone marrow transplantation of apoEo mice with apoE(o)tnf-alpha(o)... (More)
Objective - Inflammation plays an important role in atherosclerosis. One of the most potent pro-inflammatory cytokines is tumor necrosis factor-alpha (TNF-alpha), a cytokine identified to have a pathogenic role in chronic inflammatory diseases such as rheumatoid arthritis ( RA). The aim of the study was to evaluate the importance of TNF-alpha in atherogenesis. Methods and Results - Mice deficient in both apolipoprotein E (apoE) and TNF-alpha were compared regarding their atherosclerotic burden. Mice were fed a Western-style diet (WD) or normal chow. Mice deficient in both apoE and TNF-alpha exhibited a 50% ( P = 0.035) reduction of relative lesion size after 10 weeks of WD. Bone marrow transplantation of apoEo mice with apoE(o)tnf-alpha(o) bone marrow resulted in a 83% ( P = 0.021) reduction after 25 weeks on WD. In apoE knockout mice treated with recombinant soluble TNF receptor I releasing pellets, there was a reduction in relative lesion size after 25 weeks of 75% ( P = 0.018). Conclusions - These findings demonstrate that TNF-alpha is actively involved in the progression of atherosclerosis. Accordingly, TNF-alpha represents a possible target for prevention of atherosclerosis. This may be of particular importance in rheumatoid arthritis because these patients have an increased risk for cardiovascular disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, TNF-alpha, genetically altered mice
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
24
issue
11
pages
2137 - 2142
publisher
American Heart Association
external identifiers
  • pmid:15345516
  • wos:000224900300025
  • scopus:8344275053
ISSN
1524-4636
DOI
10.1161/01.ATV.0000143933.20616.1b
language
English
LU publication?
yes
id
8ba40212-de8b-4e29-b5ea-ed5a5d8735d4 (old id 127617)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15345516&dopt=Abstract
date added to LUP
2007-07-16 15:04:17
date last changed
2017-12-17 03:27:38
@article{8ba40212-de8b-4e29-b5ea-ed5a5d8735d4,
  abstract     = {Objective - Inflammation plays an important role in atherosclerosis. One of the most potent pro-inflammatory cytokines is tumor necrosis factor-alpha (TNF-alpha), a cytokine identified to have a pathogenic role in chronic inflammatory diseases such as rheumatoid arthritis ( RA). The aim of the study was to evaluate the importance of TNF-alpha in atherogenesis. Methods and Results - Mice deficient in both apolipoprotein E (apoE) and TNF-alpha were compared regarding their atherosclerotic burden. Mice were fed a Western-style diet (WD) or normal chow. Mice deficient in both apoE and TNF-alpha exhibited a 50% ( P = 0.035) reduction of relative lesion size after 10 weeks of WD. Bone marrow transplantation of apoEo mice with apoE(o)tnf-alpha(o) bone marrow resulted in a 83% ( P = 0.021) reduction after 25 weeks on WD. In apoE knockout mice treated with recombinant soluble TNF receptor I releasing pellets, there was a reduction in relative lesion size after 25 weeks of 75% ( P = 0.018). Conclusions - These findings demonstrate that TNF-alpha is actively involved in the progression of atherosclerosis. Accordingly, TNF-alpha represents a possible target for prevention of atherosclerosis. This may be of particular importance in rheumatoid arthritis because these patients have an increased risk for cardiovascular disease.},
  author       = {Brånén, Lena and Hovgaard, Lars and Nitulescu, Mihaela and Bengtsson, Eva and Nilsson, Jan and Jovinge, Stefan},
  issn         = {1524-4636},
  keyword      = {atherosclerosis,TNF-alpha,genetically altered mice},
  language     = {eng},
  number       = {11},
  pages        = {2137--2142},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Inhibition of Tumor Necrosis Factor-{alpha} Reduces Atherosclerosis in Apolipoprotein E Knockout Mice.},
  url          = {http://dx.doi.org/10.1161/01.ATV.0000143933.20616.1b},
  volume       = {24},
  year         = {2004},
}