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Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms
The increased synthesis of matrix metalloproteinases (MMPs) by aortic smooth muscle cells (SMCs) is thought to be involved in the etiopathogenesis of abdominal aortic aneurysms (AAAs), but the functional regulation and the activation states of these MMPs remain unclear. In this study, we assessed th...
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Published in: | Journal of vascular surgery 2002-03, Vol.35 (3), p.539-546 |
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container_title | Journal of vascular surgery |
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creator | Annabi, Borhane Shédid, Daniel Ghosn, Pierre Kenigsberg, Rhoda L. Desrosiers, Richard R. Bojanowski, Michel W. Beaulieu, Edith Nassif, Edgar Moumdjian, Robert Béliveau, Richard |
description | The increased synthesis of matrix metalloproteinases (MMPs) by aortic smooth muscle cells (SMCs) is thought to be involved in the etiopathogenesis of abdominal aortic aneurysms (AAAs), but the functional regulation and the activation states of these MMPs remain unclear. In this study, we assessed the expression levels and the functional regulation of several MMPs in the pathogenesis of AAAs.
Human healthy aorta and AAA specimens were homogenized, and the proteolytic activities of MMP-2 and MMP-9 and of the macrophage metalloelastase (MMP-12) were assessed with zymography. Protein expression of MMP-1, MMP-12, membrane-type 1 MMP (MT1-MMP), tissue inhibitor of MMP 1 (TIMP-1), TIMP-2, TIMP-3, α-actin, and β-actin was analyzed with electrophoresis on sodium dodecyl sulfate gels and immunoblotting.
MMP-1, MMP-9, and MMP-12 zymogen levels and proteolytic activities were increased in AAAs when compared with healthy aorta. A severe reduction in a-actin-positive vascular SMCs was observed in all the AAA specimens and was correlated with an increase in TIMP-3 but not TIMP-1 or TIMP-2 potential activities. Although pro-MMP2 activity was decreased, the extent of activated MMP-2 remained unaffected in the AAAs. In accordance with this result, a highly activated MTI-MMP form was also observed in AAAs.
These data suggest that chronic aortic wall inflammation is mediated by macrophage infiltration, which may account for the destruction of medial elastin, as reflected by SMC down regulation, through increased levels of active MMP-1 and MMP-12. Moreover, altered MTI-MMP proteolytic turnover and differential regulation of TIMP expression in AAAs suggest that tight regulatory mechanisms are involved in the molecular regulation of MMP activation processes in the pathogenesis of AAAs. |
doi_str_mv | 10.1067/mva.2002.121124 |
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Human healthy aorta and AAA specimens were homogenized, and the proteolytic activities of MMP-2 and MMP-9 and of the macrophage metalloelastase (MMP-12) were assessed with zymography. Protein expression of MMP-1, MMP-12, membrane-type 1 MMP (MT1-MMP), tissue inhibitor of MMP 1 (TIMP-1), TIMP-2, TIMP-3, α-actin, and β-actin was analyzed with electrophoresis on sodium dodecyl sulfate gels and immunoblotting.
MMP-1, MMP-9, and MMP-12 zymogen levels and proteolytic activities were increased in AAAs when compared with healthy aorta. A severe reduction in a-actin-positive vascular SMCs was observed in all the AAA specimens and was correlated with an increase in TIMP-3 but not TIMP-1 or TIMP-2 potential activities. Although pro-MMP2 activity was decreased, the extent of activated MMP-2 remained unaffected in the AAAs. In accordance with this result, a highly activated MTI-MMP form was also observed in AAAs.
These data suggest that chronic aortic wall inflammation is mediated by macrophage infiltration, which may account for the destruction of medial elastin, as reflected by SMC down regulation, through increased levels of active MMP-1 and MMP-12. Moreover, altered MTI-MMP proteolytic turnover and differential regulation of TIMP expression in AAAs suggest that tight regulatory mechanisms are involved in the molecular regulation of MMP activation processes in the pathogenesis of AAAs.</description><identifier>ISSN: 0741-5214</identifier><identifier>EISSN: 1097-6809</identifier><identifier>DOI: 10.1067/mva.2002.121124</identifier><identifier>PMID: 11877705</identifier><identifier>CODEN: JVSUES</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Actins - metabolism ; Aged ; Aged, 80 and over ; Aorta - enzymology ; Aortic Aneurysm, Abdominal - complications ; Aortic Aneurysm, Abdominal - enzymology ; Aortic Rupture - complications ; Aortic Rupture - enzymology ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Collagenases - physiology ; Diseases of the aorta ; Enzyme Precursors - physiology ; Female ; Humans ; Macrophages - enzymology ; Male ; Matrix Metalloproteinase 1 ; Matrix Metalloproteinases - physiology ; Medical sciences ; Middle Aged ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - enzymology ; Protein Isoforms - metabolism</subject><ispartof>Journal of vascular surgery, 2002-03, Vol.35 (3), p.539-546</ispartof><rights>2002 The Society for Vascular Surgery and The American Association for Vascular Surgery</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-13999531628065bacecc7534ac3a6fcd4c0b2a084de7e09b632985f86782ea0e3</citedby><cites>FETCH-LOGICAL-c482t-13999531628065bacecc7534ac3a6fcd4c0b2a084de7e09b632985f86782ea0e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13567005$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11877705$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Annabi, Borhane</creatorcontrib><creatorcontrib>Shédid, Daniel</creatorcontrib><creatorcontrib>Ghosn, Pierre</creatorcontrib><creatorcontrib>Kenigsberg, Rhoda L.</creatorcontrib><creatorcontrib>Desrosiers, Richard R.</creatorcontrib><creatorcontrib>Bojanowski, Michel W.</creatorcontrib><creatorcontrib>Beaulieu, Edith</creatorcontrib><creatorcontrib>Nassif, Edgar</creatorcontrib><creatorcontrib>Moumdjian, Robert</creatorcontrib><creatorcontrib>Béliveau, Richard</creatorcontrib><title>Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms</title><title>Journal of vascular surgery</title><addtitle>J Vasc Surg</addtitle><description>The increased synthesis of matrix metalloproteinases (MMPs) by aortic smooth muscle cells (SMCs) is thought to be involved in the etiopathogenesis of abdominal aortic aneurysms (AAAs), but the functional regulation and the activation states of these MMPs remain unclear. In this study, we assessed the expression levels and the functional regulation of several MMPs in the pathogenesis of AAAs.
Human healthy aorta and AAA specimens were homogenized, and the proteolytic activities of MMP-2 and MMP-9 and of the macrophage metalloelastase (MMP-12) were assessed with zymography. Protein expression of MMP-1, MMP-12, membrane-type 1 MMP (MT1-MMP), tissue inhibitor of MMP 1 (TIMP-1), TIMP-2, TIMP-3, α-actin, and β-actin was analyzed with electrophoresis on sodium dodecyl sulfate gels and immunoblotting.
MMP-1, MMP-9, and MMP-12 zymogen levels and proteolytic activities were increased in AAAs when compared with healthy aorta. A severe reduction in a-actin-positive vascular SMCs was observed in all the AAA specimens and was correlated with an increase in TIMP-3 but not TIMP-1 or TIMP-2 potential activities. Although pro-MMP2 activity was decreased, the extent of activated MMP-2 remained unaffected in the AAAs. In accordance with this result, a highly activated MTI-MMP form was also observed in AAAs.
These data suggest that chronic aortic wall inflammation is mediated by macrophage infiltration, which may account for the destruction of medial elastin, as reflected by SMC down regulation, through increased levels of active MMP-1 and MMP-12. Moreover, altered MTI-MMP proteolytic turnover and differential regulation of TIMP expression in AAAs suggest that tight regulatory mechanisms are involved in the molecular regulation of MMP activation processes in the pathogenesis of AAAs.</description><subject>Actins - metabolism</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aorta - enzymology</subject><subject>Aortic Aneurysm, Abdominal - complications</subject><subject>Aortic Aneurysm, Abdominal - enzymology</subject><subject>Aortic Rupture - complications</subject><subject>Aortic Rupture - enzymology</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Collagenases - physiology</subject><subject>Diseases of the aorta</subject><subject>Enzyme Precursors - physiology</subject><subject>Female</subject><subject>Humans</subject><subject>Macrophages - enzymology</subject><subject>Male</subject><subject>Matrix Metalloproteinase 1</subject><subject>Matrix Metalloproteinases - physiology</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - enzymology</subject><subject>Protein Isoforms - metabolism</subject><issn>0741-5214</issn><issn>1097-6809</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNp1kM9v1DAQha2Kql0KZ27IF7hlO3ac2D6ill9SJS5wQ7ImzgQZOXGxnVX735OyK_XEaQ7zvaenj7E3AvYCen09H3AvAeReSCGkOmM7AVY3vQH7gu1AK9F0UqhL9rKU3wBCdEZfsEshjNYauh37eRumiTItNWDkmX6tEWtIC08Tn7Hm8MBnqhhjus-pUliwEEdfwyHUQIWHheMwpnl7RI4p1-A5LrTmxzKXV-x8wljo9elesR-fPn6_-dLcffv89ebDXeOVkbURrbW2a0UvDfTdgJ68112r0LfYT35UHgaJYNRImsAOfSut6SbTayMJgdor9v7Yu238s1Kpbg7FU4zbkrQWp4WyClqzgddH0OdUSqbJ3ecwY350AtyTULcJdU9C3VHolnh7ql6HmcZn_mRwA96dACwe45Rx8aE8c23Xa_jH2SNHm4hDoOyKD7R4GkMmX92Ywn9H_AWKU5MB</recordid><startdate>20020301</startdate><enddate>20020301</enddate><creator>Annabi, Borhane</creator><creator>Shédid, Daniel</creator><creator>Ghosn, Pierre</creator><creator>Kenigsberg, Rhoda L.</creator><creator>Desrosiers, Richard R.</creator><creator>Bojanowski, Michel W.</creator><creator>Beaulieu, Edith</creator><creator>Nassif, Edgar</creator><creator>Moumdjian, Robert</creator><creator>Béliveau, Richard</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>20020301</creationdate><title>Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms</title><author>Annabi, Borhane ; Shédid, Daniel ; Ghosn, Pierre ; Kenigsberg, Rhoda L. ; Desrosiers, Richard R. ; Bojanowski, Michel W. ; Beaulieu, Edith ; Nassif, Edgar ; Moumdjian, Robert ; Béliveau, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-13999531628065bacecc7534ac3a6fcd4c0b2a084de7e09b632985f86782ea0e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Actins - metabolism</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aorta - enzymology</topic><topic>Aortic Aneurysm, Abdominal - complications</topic><topic>Aortic Aneurysm, Abdominal - enzymology</topic><topic>Aortic Rupture - complications</topic><topic>Aortic Rupture - enzymology</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Collagenases - physiology</topic><topic>Diseases of the aorta</topic><topic>Enzyme Precursors - physiology</topic><topic>Female</topic><topic>Humans</topic><topic>Macrophages - enzymology</topic><topic>Male</topic><topic>Matrix Metalloproteinase 1</topic><topic>Matrix Metalloproteinases - physiology</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - enzymology</topic><topic>Protein Isoforms - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Annabi, Borhane</creatorcontrib><creatorcontrib>Shédid, Daniel</creatorcontrib><creatorcontrib>Ghosn, Pierre</creatorcontrib><creatorcontrib>Kenigsberg, Rhoda L.</creatorcontrib><creatorcontrib>Desrosiers, Richard R.</creatorcontrib><creatorcontrib>Bojanowski, Michel W.</creatorcontrib><creatorcontrib>Beaulieu, Edith</creatorcontrib><creatorcontrib>Nassif, Edgar</creatorcontrib><creatorcontrib>Moumdjian, Robert</creatorcontrib><creatorcontrib>Béliveau, Richard</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Journal of vascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Annabi, Borhane</au><au>Shédid, Daniel</au><au>Ghosn, Pierre</au><au>Kenigsberg, Rhoda L.</au><au>Desrosiers, Richard R.</au><au>Bojanowski, Michel W.</au><au>Beaulieu, Edith</au><au>Nassif, Edgar</au><au>Moumdjian, Robert</au><au>Béliveau, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms</atitle><jtitle>Journal of vascular surgery</jtitle><addtitle>J Vasc Surg</addtitle><date>2002-03-01</date><risdate>2002</risdate><volume>35</volume><issue>3</issue><spage>539</spage><epage>546</epage><pages>539-546</pages><issn>0741-5214</issn><eissn>1097-6809</eissn><coden>JVSUES</coden><abstract>The increased synthesis of matrix metalloproteinases (MMPs) by aortic smooth muscle cells (SMCs) is thought to be involved in the etiopathogenesis of abdominal aortic aneurysms (AAAs), but the functional regulation and the activation states of these MMPs remain unclear. In this study, we assessed the expression levels and the functional regulation of several MMPs in the pathogenesis of AAAs.
Human healthy aorta and AAA specimens were homogenized, and the proteolytic activities of MMP-2 and MMP-9 and of the macrophage metalloelastase (MMP-12) were assessed with zymography. Protein expression of MMP-1, MMP-12, membrane-type 1 MMP (MT1-MMP), tissue inhibitor of MMP 1 (TIMP-1), TIMP-2, TIMP-3, α-actin, and β-actin was analyzed with electrophoresis on sodium dodecyl sulfate gels and immunoblotting.
MMP-1, MMP-9, and MMP-12 zymogen levels and proteolytic activities were increased in AAAs when compared with healthy aorta. A severe reduction in a-actin-positive vascular SMCs was observed in all the AAA specimens and was correlated with an increase in TIMP-3 but not TIMP-1 or TIMP-2 potential activities. Although pro-MMP2 activity was decreased, the extent of activated MMP-2 remained unaffected in the AAAs. In accordance with this result, a highly activated MTI-MMP form was also observed in AAAs.
These data suggest that chronic aortic wall inflammation is mediated by macrophage infiltration, which may account for the destruction of medial elastin, as reflected by SMC down regulation, through increased levels of active MMP-1 and MMP-12. Moreover, altered MTI-MMP proteolytic turnover and differential regulation of TIMP expression in AAAs suggest that tight regulatory mechanisms are involved in the molecular regulation of MMP activation processes in the pathogenesis of AAAs.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>11877705</pmid><doi>10.1067/mva.2002.121124</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Actins - metabolism Aged Aged, 80 and over Aorta - enzymology Aortic Aneurysm, Abdominal - complications Aortic Aneurysm, Abdominal - enzymology Aortic Rupture - complications Aortic Rupture - enzymology Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Collagenases - physiology Diseases of the aorta Enzyme Precursors - physiology Female Humans Macrophages - enzymology Male Matrix Metalloproteinase 1 Matrix Metalloproteinases - physiology Medical sciences Middle Aged Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - enzymology Protein Isoforms - metabolism |
title | Differential regulation of matrix metalloproteinase activities in abdominal aortic aneurysms |
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