Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation
Primary varicose veins are functionally characterized by venous back‐flow and blood stagnation in the upright position. Dilatation and tortuosity provide evidence for progressive venous wall remodelling, with disturbance of smooth muscle cell/extracellular matrix organization. Affected areas are not...
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| creator | Badier-Commander, Cécile Verbeuren, Tony Lebard, Christian Michel, Jean-Baptiste Jacob, Marie-Paule |
| description | Primary varicose veins are functionally characterized by venous back‐flow and blood stagnation in the upright position. Dilatation and tortuosity provide evidence for progressive venous wall remodelling, with disturbance of smooth muscle cell/extracellular matrix organization. Affected areas are not uniformly distributed, some areas being hypertrophic, whereas others are atrophic or unaffected. In 12 varicose veins and ten control veins, the proteolytic enzyme/inhibitor balance which may participate in the remodelling of the venous wall was investigated. For this purpose, the presence and enzymatic activity of matrix metalloproteinases (MMP‐2, MMP‐9), tissue inhibitors of MMPs (TIMP‐1, TIMP‐2), urokinase‐type (uPA) and tissue‐type (tPA) plasminogen activators (PAs), and plasminogen activator inhibitor‐1 (PAI‐1) were quantified by western blot and gelatin or plasminogen–casein zymography. In addition, MMP‐2, TIMP‐1, TIMP‐2, and PAI‐1 levels were measured by ELISA. A high TIMP‐1 level and a low MMP‐2 level/activity were found in varicose veins (p |
| doi_str_mv | 10.1002/1096-9896(2000)9999:9999<::AID-PATH670>3.0.CO;2-1 |
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Dilatation and tortuosity provide evidence for progressive venous wall remodelling, with disturbance of smooth muscle cell/extracellular matrix organization. Affected areas are not uniformly distributed, some areas being hypertrophic, whereas others are atrophic or unaffected. In 12 varicose veins and ten control veins, the proteolytic enzyme/inhibitor balance which may participate in the remodelling of the venous wall was investigated. For this purpose, the presence and enzymatic activity of matrix metalloproteinases (MMP‐2, MMP‐9), tissue inhibitors of MMPs (TIMP‐1, TIMP‐2), urokinase‐type (uPA) and tissue‐type (tPA) plasminogen activators (PAs), and plasminogen activator inhibitor‐1 (PAI‐1) were quantified by western blot and gelatin or plasminogen–casein zymography. In addition, MMP‐2, TIMP‐1, TIMP‐2, and PAI‐1 levels were measured by ELISA. A high TIMP‐1 level and a low MMP‐2 level/activity were found in varicose veins (p<0.005), resulting in a three‐fold increase in the TIMP‐1/MMP‐2 ratio in varicose versus control veins. Levels of PAs (uPA and tPA) as well as PAI‐1 were both lower in varicose veins (p<0.005), with minimal change in the PAI/PA ratio. These results demonstrate that varicose veins are characterized by a higher than normal TIMP/MMP ratio, which may facilitate extracellular matrix accumulation in the diseased venous wall. Copyright © 2000 John Wiley & Sons, Ltd.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/1096-9896(2000)9999:9999<::AID-PATH670>3.0.CO;2-1</identifier><identifier>PMID: 10951407</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adult ; Biological and medical sciences ; Blood and lymphatic vessels ; Blotting, Western ; Cardiology. Vascular system ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Extracellular Matrix - enzymology ; Extracellular Matrix - metabolism ; Female ; human ; Humans ; Male ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Matrix Metalloproteinases - metabolism ; Medical sciences ; Middle Aged ; MMP ; Plasminogen Activators - metabolism ; Plasminogen Inactivators - metabolism ; TIMP ; Tissue Inhibitor of Metalloproteinase-1 - metabolism ; Tissue Inhibitor of Metalloproteinase-2 - metabolism ; Tissue Inhibitor of Metalloproteinases - metabolism ; varicose veins ; Varicose Veins - enzymology ; Varicose Veins - metabolism</subject><ispartof>The Journal of pathology, 2000-09, Vol.192 (1), p.105-112</ispartof><rights>Copyright © 2000 John Wiley & Sons, Ltd.</rights><rights>2000 INIST-CNRS</rights><rights>Copyright 2000 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4250-466e43799aed3535e5fedc4b7e6fafb2063b72c33da062327379f1de45f8cde23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F1096-9896%282000%299999%3A9999%3C%3A%3AAID-PATH670%3E3.0.CO%3B2-1$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F1096-9896%282000%299999%3A9999%3C%3A%3AAID-PATH670%3E3.0.CO%3B2-1$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1474253$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10951407$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Badier-Commander, Cécile</creatorcontrib><creatorcontrib>Verbeuren, Tony</creatorcontrib><creatorcontrib>Lebard, Christian</creatorcontrib><creatorcontrib>Michel, Jean-Baptiste</creatorcontrib><creatorcontrib>Jacob, Marie-Paule</creatorcontrib><title>Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>Primary varicose veins are functionally characterized by venous back‐flow and blood stagnation in the upright position. Dilatation and tortuosity provide evidence for progressive venous wall remodelling, with disturbance of smooth muscle cell/extracellular matrix organization. Affected areas are not uniformly distributed, some areas being hypertrophic, whereas others are atrophic or unaffected. In 12 varicose veins and ten control veins, the proteolytic enzyme/inhibitor balance which may participate in the remodelling of the venous wall was investigated. For this purpose, the presence and enzymatic activity of matrix metalloproteinases (MMP‐2, MMP‐9), tissue inhibitors of MMPs (TIMP‐1, TIMP‐2), urokinase‐type (uPA) and tissue‐type (tPA) plasminogen activators (PAs), and plasminogen activator inhibitor‐1 (PAI‐1) were quantified by western blot and gelatin or plasminogen–casein zymography. In addition, MMP‐2, TIMP‐1, TIMP‐2, and PAI‐1 levels were measured by ELISA. A high TIMP‐1 level and a low MMP‐2 level/activity were found in varicose veins (p<0.005), resulting in a three‐fold increase in the TIMP‐1/MMP‐2 ratio in varicose versus control veins. Levels of PAs (uPA and tPA) as well as PAI‐1 were both lower in varicose veins (p<0.005), with minimal change in the PAI/PA ratio. These results demonstrate that varicose veins are characterized by a higher than normal TIMP/MMP ratio, which may facilitate extracellular matrix accumulation in the diseased venous wall. Copyright © 2000 John Wiley & Sons, Ltd.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blotting, Western</subject><subject>Cardiology. Vascular system</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Extracellular Matrix - enzymology</subject><subject>Extracellular Matrix - metabolism</subject><subject>Female</subject><subject>human</subject><subject>Humans</subject><subject>Male</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>MMP</subject><subject>Plasminogen Activators - metabolism</subject><subject>Plasminogen Inactivators - metabolism</subject><subject>TIMP</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinase-2 - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><subject>varicose veins</subject><subject>Varicose Veins - enzymology</subject><subject>Varicose Veins - metabolism</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEtvEzEURi0EomnhLyAvEKKLST1-TR0QUhQgiWgeSEGwsxzPHWGYR7BnSvrv8WhCYcECL67lq-PP1wchlZJxSgi9SomSibpW8iUlhFyquCZ9eT2ZTJdvk-10t5AZecPGZDzbvKJJ-gCN7u88RKOYQRPG0-wMnYfwLWYoJcRjdBYhkXKSjdDXZW09mAA53i1X26vVaou9aV2DXY1vjXe2CYBvwdVhgg0-NCG4fQkYjofS1D1Y46Lx8dx6Y6Esu9J4XJnWuyM21nZVbPTUE_SoMGWAp6f9An16_243WyQ3m_lyNr1JLKeCJFxK4CxTykDOBBMgCsgt32cgC1PsKZFsn1HLWG6IpIxmkS3SHLgorm0OlF2gF0PuwTc_OgitrlzoBzM1NF3QGU2V4IpH8OMAWh8_5aHQB-8q4-90SnSvX_cqda9S9_p1b34oWkf9-qRfM030bKMjHzOfnR7v9hXkfyUOviPw_ASYYE1ZeFNbF_5wPIsWWMR2A_bTlXD3_4P9e6zfrRibDLEutHC8jzX-u5ZRpNCf13Mtvyi5-LBe6zn7Bdnuuwo</recordid><startdate>200009</startdate><enddate>200009</enddate><creator>Badier-Commander, Cécile</creator><creator>Verbeuren, Tony</creator><creator>Lebard, Christian</creator><creator>Michel, Jean-Baptiste</creator><creator>Jacob, Marie-Paule</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><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>200009</creationdate><title>Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation</title><author>Badier-Commander, Cécile ; Verbeuren, Tony ; Lebard, Christian ; Michel, Jean-Baptiste ; Jacob, Marie-Paule</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4250-466e43799aed3535e5fedc4b7e6fafb2063b72c33da062327379f1de45f8cde23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blotting, Western</topic><topic>Cardiology. Vascular system</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Extracellular Matrix - enzymology</topic><topic>Extracellular Matrix - metabolism</topic><topic>Female</topic><topic>human</topic><topic>Humans</topic><topic>Male</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>MMP</topic><topic>Plasminogen Activators - metabolism</topic><topic>Plasminogen Inactivators - metabolism</topic><topic>TIMP</topic><topic>Tissue Inhibitor of Metalloproteinase-1 - metabolism</topic><topic>Tissue Inhibitor of Metalloproteinase-2 - metabolism</topic><topic>Tissue Inhibitor of Metalloproteinases - metabolism</topic><topic>varicose veins</topic><topic>Varicose Veins - enzymology</topic><topic>Varicose Veins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Badier-Commander, Cécile</creatorcontrib><creatorcontrib>Verbeuren, Tony</creatorcontrib><creatorcontrib>Lebard, Christian</creatorcontrib><creatorcontrib>Michel, Jean-Baptiste</creatorcontrib><creatorcontrib>Jacob, Marie-Paule</creatorcontrib><collection>Istex</collection><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>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Badier-Commander, Cécile</au><au>Verbeuren, Tony</au><au>Lebard, Christian</au><au>Michel, Jean-Baptiste</au><au>Jacob, Marie-Paule</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2000-09</date><risdate>2000</risdate><volume>192</volume><issue>1</issue><spage>105</spage><epage>112</epage><pages>105-112</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><abstract>Primary varicose veins are functionally characterized by venous back‐flow and blood stagnation in the upright position. Dilatation and tortuosity provide evidence for progressive venous wall remodelling, with disturbance of smooth muscle cell/extracellular matrix organization. Affected areas are not uniformly distributed, some areas being hypertrophic, whereas others are atrophic or unaffected. In 12 varicose veins and ten control veins, the proteolytic enzyme/inhibitor balance which may participate in the remodelling of the venous wall was investigated. For this purpose, the presence and enzymatic activity of matrix metalloproteinases (MMP‐2, MMP‐9), tissue inhibitors of MMPs (TIMP‐1, TIMP‐2), urokinase‐type (uPA) and tissue‐type (tPA) plasminogen activators (PAs), and plasminogen activator inhibitor‐1 (PAI‐1) were quantified by western blot and gelatin or plasminogen–casein zymography. In addition, MMP‐2, TIMP‐1, TIMP‐2, and PAI‐1 levels were measured by ELISA. A high TIMP‐1 level and a low MMP‐2 level/activity were found in varicose veins (p<0.005), resulting in a three‐fold increase in the TIMP‐1/MMP‐2 ratio in varicose versus control veins. Levels of PAs (uPA and tPA) as well as PAI‐1 were both lower in varicose veins (p<0.005), with minimal change in the PAI/PA ratio. These results demonstrate that varicose veins are characterized by a higher than normal TIMP/MMP ratio, which may facilitate extracellular matrix accumulation in the diseased venous wall. Copyright © 2000 John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>10951407</pmid><doi>10.1002/1096-9896(2000)9999:9999<::AID-PATH670>3.0.CO;2-1</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Biological and medical sciences Blood and lymphatic vessels Blotting, Western Cardiology. Vascular system Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Extracellular Matrix - enzymology Extracellular Matrix - metabolism Female human Humans Male Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Matrix Metalloproteinases - metabolism Medical sciences Middle Aged MMP Plasminogen Activators - metabolism Plasminogen Inactivators - metabolism TIMP Tissue Inhibitor of Metalloproteinase-1 - metabolism Tissue Inhibitor of Metalloproteinase-2 - metabolism Tissue Inhibitor of Metalloproteinases - metabolism varicose veins Varicose Veins - enzymology Varicose Veins - metabolism |
| title | Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation |
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