Document Detail


Exclusive expression of transmembrane TNF-alpha in mice reduces the inflammatory response in early lipid lesions of aortic sinus.
MedLine Citation:
PMID:  15019530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the effect of transmembrane form of tumor necrosis factor-alpha (TNF) on atherosclerosis in mice. We compared the development of early atherosclerotic lesions in the aortic sinus of (1) TNF-deficient mice that express only a non-cleavable transmembrane form of TNF (tmTNF), (2) wild-type (WT) C57BL/6 mice, and (3) TNF-deficient mice (TNF(-/-)). All mice were fed an atherogenic diet for 20 weeks. Lipid deposition was the most prominent in WT mice (25030 +/- 5693 microm2), tended to be lower in tmTNF mice (13640+/- 2190 microm2, P > 0.05 versus WT mice) and rare in TNF(-/-) mice (1408 +/- 513 microm2, P < 0.05 versus tmTNF and P < 0.01 versus WT). Macrophage accumulation was five-fold lower (P < 0.05) in tmTNF than in WT mice. In addition, the alpha-actin immuno-reactivity of medial smooth muscle cells remained intact in tmTNF mice but not in WT mice. In WT mice, the plasma lipid profile was significantly more atherogenic than that of TNF(-/-) mice (P < 0.05), but not significantly different from that of tmTNF mice (P > 0.05). These results indicated that in contrast to TNF(-/-) mice, mice expressing exclusively tmTNF were not completely protected from early atherosclerotic lesion formation, although their lesions have a less inflammatory state than those of WT mice, which underlines the stronger proinflammatory potential of soluble TNF.
Authors:
Matthias Canault; Franck Peiretti; Christoph Mueller; Francis Kopp; Pierre Morange; Sylvia Rihs; Henri Portugal; Irène Juhan-Vague; Gilles Nalbone
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Atherosclerosis     Volume:  172     ISSN:  0021-9150     ISO Abbreviation:  Atherosclerosis     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-03-15     Completed Date:  2004-06-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  211-8     Citation Subset:  IM    
Affiliation:
Faculté de Médecine, INSERM EPI 99-36, 27 Bd. Jean Moulin, 13385 Marseilles 5, France.
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MeSH Terms
Descriptor/Qualifier:
Actins / analysis
Animals
Arteriosclerosis / blood,  metabolism*
Immunohistochemistry
Lipid Metabolism
Macrophages / pathology
Mice
Mice, Transgenic
Muscle, Smooth / chemistry
Sinus of Valsalva / chemistry*,  pathology
Tumor Necrosis Factor-alpha / analysis*,  physiology
Chemical
Reg. No./Substance:
0/Actins; 0/Tumor Necrosis Factor-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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