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 |
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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 |
format | Article |
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−/−). 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<0.05 versus tmTNF and
P<0.01 versus WT). Macrophage accumulation was five-fold lower (
P<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<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.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2003.10.004</identifier><identifier>PMID: 15019530</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>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</subject><ispartof>Atherosclerosis, 2004-02, Vol.172 (2), p.211-218</ispartof><rights>2003 Elsevier Ireland Ltd</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-a578316875ff9cfc000dbfe9ee404177bc5d25d09698ae1e6cc9db98ef59f2ae3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.atherosclerosis.2003.10.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15433335$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15019530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Exclusive expression of transmembrane TNF-α in mice reduces the inflammatory response in early lipid lesions of aortic sinus</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><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<0.05 versus tmTNF and
P<0.01 versus WT). Macrophage accumulation was five-fold lower (
P<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<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.</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>0.05 versus WT mice) and rare in TNF
−/− mice (1408±513
μm
2,
P<0.05 versus tmTNF and
P<0.01 versus WT). Macrophage accumulation was five-fold lower (
P<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<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.</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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