Exclusive expression of transmembrane TNF-α in mice reduces the inflammatory response in early lipid lesions of aortic sinus

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-t...

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Veröffentlicht in:Atherosclerosis 2004-02, Vol.172 (2), p.211-218
Hauptverfasser: Canault, Matthias, Peiretti, Franck, Mueller, Christoph, Kopp, Francis, Morange, Pierre, Rihs, Sylvia, Portugal, Henri, Juhan-Vague, Irène, Nalbone, Gilles
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container_end_page 218
container_issue 2
container_start_page 211
container_title Atherosclerosis
container_volume 172
creator Canault, Matthias
Peiretti, Franck
Mueller, Christoph
Kopp, Francis
Morange, Pierre
Rihs, Sylvia
Portugal, Henri
Juhan-Vague, Irène
Nalbone, Gilles
description 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 μm 2), tended to be lower in tmTNF mice (13640±2190 μm 2, P>0.05 versus WT mice) and rare in TNF −/− mice (1408±513 μm 2, P
doi_str_mv 10.1016/j.atherosclerosis.2003.10.004
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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 μm 2), tended to be lower in tmTNF mice (13640±2190 μm 2, P&gt;0.05 versus WT mice) and rare in TNF −/− mice (1408±513 μm 2, P&lt;0.05 versus tmTNF and P&lt;0.01 versus WT). Macrophage accumulation was five-fold lower ( P&lt;0.01) in tmTNF than in WT mice. In addition, the α-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&lt;0.05), but not significantly different from that of tmTNF mice ( P&gt;0.05). 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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 μm 2), tended to be lower in tmTNF mice (13640±2190 μm 2, P&gt;0.05 versus WT mice) and rare in TNF −/− mice (1408±513 μm 2, P&lt;0.05 versus tmTNF and P&lt;0.01 versus WT). Macrophage accumulation was five-fold lower ( P&lt;0.01) in tmTNF than in WT mice. In addition, the α-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&lt;0.05), but not significantly different from that of tmTNF mice ( P&gt;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.</description><subject>Actins - analysis</subject><subject>Animals</subject><subject>Arteriosclerosis - blood</subject><subject>Arteriosclerosis - metabolism</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Dyslipidemia</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Lipid Metabolism</subject><subject>Macrophages - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Muscle, Smooth - chemistry</subject><subject>Sinus of Valsalva - chemistry</subject><subject>Sinus of Valsalva - pathology</subject><subject>TNF-α</subject><subject>Transgenic mice</subject><subject>Tumor Necrosis Factor-alpha - analysis</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1u1DAQgC0EotvCKyBfyi2Lvfn1gQOq2lKpgks5W449Fl45cfAkVffQh-JFeCYm2pUqccIHW5r5ZjzzMXYpxVYK2Xzab838E3JCG9c74HYnREm5rRDVK7aRXasKWXXVa7YRYicLJWtxxs4R94KIVnZv2RmFpKpLsWHP1082LhgegcPTlAExpJEnz-dsRhxg6OkF_vDtpvjzm4eRD8ECz-AWC8hpEor5aIbBzCkfKIFTGnGNcjA5HngMU3A8wtoX18Ym5TlYjmFc8B17401EeH96L9iPm-uHq6_F_ffbu6sv94WtZD0Xpm67UjZdW3uvrLe0iOs9KIBKVLJte1u7Xe2EalRnQEJjrXK96sDXyu8MlBfs47HvlNOvBXDWQ0ALMdJuaUHdyrZshFAEfj6CltxiBq-nHAaTD1oKvfrXe_2Pf736X9Nkl-o_nD5a-gHcS_VJOAGXJ8CgNdGTXUs9XriqpFMTd3vkgLQ8BsgabYDRggsZ7KxdCv850l-pmbG0</recordid><startdate>20040201</startdate><enddate>20040201</enddate><creator>Canault, Matthias</creator><creator>Peiretti, Franck</creator><creator>Mueller, Christoph</creator><creator>Kopp, Francis</creator><creator>Morange, Pierre</creator><creator>Rihs, Sylvia</creator><creator>Portugal, Henri</creator><creator>Juhan-Vague, Irène</creator><creator>Nalbone, Gilles</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040201</creationdate><title>Exclusive expression of transmembrane TNF-α in mice reduces the inflammatory response in early lipid lesions of aortic sinus</title><author>Canault, Matthias ; Peiretti, Franck ; Mueller, Christoph ; Kopp, Francis ; Morange, Pierre ; Rihs, Sylvia ; Portugal, Henri ; Juhan-Vague, Irène ; Nalbone, Gilles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-a578316875ff9cfc000dbfe9ee404177bc5d25d09698ae1e6cc9db98ef59f2ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Actins - analysis</topic><topic>Animals</topic><topic>Arteriosclerosis - blood</topic><topic>Arteriosclerosis - metabolism</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Dyslipidemia</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Lipid Metabolism</topic><topic>Macrophages - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Muscle, Smooth - chemistry</topic><topic>Sinus of Valsalva - chemistry</topic><topic>Sinus of Valsalva - pathology</topic><topic>TNF-α</topic><topic>Transgenic mice</topic><topic>Tumor Necrosis Factor-alpha - analysis</topic><topic>Tumor Necrosis Factor-alpha - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Canault, Matthias</creatorcontrib><creatorcontrib>Peiretti, Franck</creatorcontrib><creatorcontrib>Mueller, Christoph</creatorcontrib><creatorcontrib>Kopp, Francis</creatorcontrib><creatorcontrib>Morange, Pierre</creatorcontrib><creatorcontrib>Rihs, Sylvia</creatorcontrib><creatorcontrib>Portugal, Henri</creatorcontrib><creatorcontrib>Juhan-Vague, Irène</creatorcontrib><creatorcontrib>Nalbone, Gilles</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Canault, Matthias</au><au>Peiretti, Franck</au><au>Mueller, Christoph</au><au>Kopp, Francis</au><au>Morange, Pierre</au><au>Rihs, Sylvia</au><au>Portugal, Henri</au><au>Juhan-Vague, Irène</au><au>Nalbone, Gilles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exclusive expression of transmembrane TNF-α in mice reduces the inflammatory response in early lipid lesions of aortic sinus</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2004-02-01</date><risdate>2004</risdate><volume>172</volume><issue>2</issue><spage>211</spage><epage>218</epage><pages>211-218</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>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 μm 2), tended to be lower in tmTNF mice (13640±2190 μm 2, P&gt;0.05 versus WT mice) and rare in TNF −/− mice (1408±513 μm 2, P&lt;0.05 versus tmTNF and P&lt;0.01 versus WT). Macrophage accumulation was five-fold lower ( P&lt;0.01) in tmTNF than in WT mice. In addition, the α-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&lt;0.05), but not significantly different from that of tmTNF mice ( P&gt;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.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>15019530</pmid><doi>10.1016/j.atherosclerosis.2003.10.004</doi><tpages>8</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects Actins - analysis
Animals
Arteriosclerosis - blood
Arteriosclerosis - metabolism
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Dyslipidemia
Immunohistochemistry
Inflammation
Lipid Metabolism
Macrophages - pathology
Medical sciences
Mice
Mice, Transgenic
Muscle, Smooth - chemistry
Sinus of Valsalva - chemistry
Sinus of Valsalva - pathology
TNF-α
Transgenic mice
Tumor Necrosis Factor-alpha - analysis
Tumor Necrosis Factor-alpha - physiology
title Exclusive expression of transmembrane TNF-α in mice reduces the inflammatory response in early lipid lesions of aortic sinus
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