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Effect of Hormones on Matrix Metalloproteinases Gene Regulation in Human Aortic Smooth Muscle Cells
Background Postmenopausal women receiving hormone replacement therapy have more adverse outcomes after vascular reconstructions. Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key grou...
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| Published in: | The Journal of surgical research 2008-07, Vol.148 (1), p.94-99 |
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| creator | Grandas, Oscar H., M.D Mountain, Deidra J.H., Ph.D Kirkpatrick, Stacy S., B.S Rudrapatna, Vivek S., M.D Cassada, David C., M.D Stevens, Scott L., M.D Freeman, Michael B., M.D Goldman, Mitchell H., M.D |
| description | Background Postmenopausal women receiving hormone replacement therapy have more adverse outcomes after vascular reconstructions. Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key group of enzymes involved in vascular remodeling are matrix metalloproteinases (MMPs). Here we studied the effect of estrogen (Est) and progesterone (Prog) on MMP gene expression in human VSMCs. Methods and results VSMCs were incubated with Est (5 ng/mL), Prog (50 ng/mL), Est+Prog combination (Est/Prog), and interleukin-1β (100 U/mL; IL-1β). Gene array analysis indicated Est+IL-1β increased the expression of MMP-3. Reverse transcriptase-polymer chain reaction (RT-PCR) analyses revealed MMP-3 mRNA levels were significantly increased by Est/Prog+IL-1β treatment. However, Western blot and further RT-PCR analyses indicated no change in MMP-3 in response to hormones alone. RT-PCR analyses revealed membrane type 1 (MT1)-MMP mRNA levels, not MMP-2 or tissue inhibitor of MMP (TIMP), were significantly increased by Est/Prog+IL-1β, and Western blot analyses confirmed a significant increase in MT1-MMP protein in response to Est alone. Conclusion Estrogen and progesterone affect the MMP pathway of VSMCs via isoform specific mechanisms and may lead to unbalanced MMP regulation. Estrogen up-regulates MT1-MMP without a corresponding increase in TIMP-2, known activator and inhibitor of MMP-2, respectively. Additionally, estrogen up-regulates MMP-3 only in the presence of IL-1β. This differential regulation, combined with case-specific variations in degree of inflammatory response, may explain why some women receiving exogenous hormone therapy at the time of vascular interventions are more susceptible to complications. |
| doi_str_mv | 10.1016/j.jss.2008.03.003 |
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Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key group of enzymes involved in vascular remodeling are matrix metalloproteinases (MMPs). Here we studied the effect of estrogen (Est) and progesterone (Prog) on MMP gene expression in human VSMCs. Methods and results VSMCs were incubated with Est (5 ng/mL), Prog (50 ng/mL), Est+Prog combination (Est/Prog), and interleukin-1β (100 U/mL; IL-1β). Gene array analysis indicated Est+IL-1β increased the expression of MMP-3. Reverse transcriptase-polymer chain reaction (RT-PCR) analyses revealed MMP-3 mRNA levels were significantly increased by Est/Prog+IL-1β treatment. However, Western blot and further RT-PCR analyses indicated no change in MMP-3 in response to hormones alone. RT-PCR analyses revealed membrane type 1 (MT1)-MMP mRNA levels, not MMP-2 or tissue inhibitor of MMP (TIMP), were significantly increased by Est/Prog+IL-1β, and Western blot analyses confirmed a significant increase in MT1-MMP protein in response to Est alone. Conclusion Estrogen and progesterone affect the MMP pathway of VSMCs via isoform specific mechanisms and may lead to unbalanced MMP regulation. Estrogen up-regulates MT1-MMP without a corresponding increase in TIMP-2, known activator and inhibitor of MMP-2, respectively. Additionally, estrogen up-regulates MMP-3 only in the presence of IL-1β. This differential regulation, combined with case-specific variations in degree of inflammatory response, may explain why some women receiving exogenous hormone therapy at the time of vascular interventions are more susceptible to complications.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2008.03.003</identifier><identifier>PMID: 18570937</identifier><identifier>CODEN: JSGRA2</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Biological and medical sciences ; Blotting, Western ; Cell Culture Techniques ; estrogen ; Estrogens - pharmacology ; Female ; Gene Expression - drug effects ; General aspects ; HRT ; Humans ; Interleukin-1beta - pharmacology ; Matrix Metalloproteinase 14 - metabolism ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 3 - metabolism ; Matrix Metalloproteinases - metabolism ; Medical sciences ; MMP ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - enzymology ; Postmenopause ; Progesterone - pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Surgery ; Tissue Inhibitor of Metalloproteinases - metabolism ; Up-Regulation ; vascular remodeling ; VSMC</subject><ispartof>The Journal of surgical research, 2008-07, Vol.148 (1), p.94-99</ispartof><rights>Elsevier Inc.</rights><rights>2008 Elsevier Inc.</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c351t-961701c06a9e8172f1f05cbf78a503dd56b8ed91157ac9955d0a689f6f60dc0b3</citedby><cites>FETCH-LOGICAL-c351t-961701c06a9e8172f1f05cbf78a503dd56b8ed91157ac9955d0a689f6f60dc0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20470420$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18570937$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Grandas, Oscar H., M.D</creatorcontrib><creatorcontrib>Mountain, Deidra J.H., Ph.D</creatorcontrib><creatorcontrib>Kirkpatrick, Stacy S., B.S</creatorcontrib><creatorcontrib>Rudrapatna, Vivek S., M.D</creatorcontrib><creatorcontrib>Cassada, David C., M.D</creatorcontrib><creatorcontrib>Stevens, Scott L., M.D</creatorcontrib><creatorcontrib>Freeman, Michael B., M.D</creatorcontrib><creatorcontrib>Goldman, Mitchell H., M.D</creatorcontrib><title>Effect of Hormones on Matrix Metalloproteinases Gene Regulation in Human Aortic Smooth Muscle Cells</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Background Postmenopausal women receiving hormone replacement therapy have more adverse outcomes after vascular reconstructions. Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key group of enzymes involved in vascular remodeling are matrix metalloproteinases (MMPs). Here we studied the effect of estrogen (Est) and progesterone (Prog) on MMP gene expression in human VSMCs. Methods and results VSMCs were incubated with Est (5 ng/mL), Prog (50 ng/mL), Est+Prog combination (Est/Prog), and interleukin-1β (100 U/mL; IL-1β). Gene array analysis indicated Est+IL-1β increased the expression of MMP-3. Reverse transcriptase-polymer chain reaction (RT-PCR) analyses revealed MMP-3 mRNA levels were significantly increased by Est/Prog+IL-1β treatment. However, Western blot and further RT-PCR analyses indicated no change in MMP-3 in response to hormones alone. RT-PCR analyses revealed membrane type 1 (MT1)-MMP mRNA levels, not MMP-2 or tissue inhibitor of MMP (TIMP), were significantly increased by Est/Prog+IL-1β, and Western blot analyses confirmed a significant increase in MT1-MMP protein in response to Est alone. Conclusion Estrogen and progesterone affect the MMP pathway of VSMCs via isoform specific mechanisms and may lead to unbalanced MMP regulation. Estrogen up-regulates MT1-MMP without a corresponding increase in TIMP-2, known activator and inhibitor of MMP-2, respectively. Additionally, estrogen up-regulates MMP-3 only in the presence of IL-1β. This differential regulation, combined with case-specific variations in degree of inflammatory response, may explain why some women receiving exogenous hormone therapy at the time of vascular interventions are more susceptible to complications.</description><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell Culture Techniques</subject><subject>estrogen</subject><subject>Estrogens - pharmacology</subject><subject>Female</subject><subject>Gene Expression - drug effects</subject><subject>General aspects</subject><subject>HRT</subject><subject>Humans</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Matrix Metalloproteinase 14 - metabolism</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 3 - metabolism</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical sciences</subject><subject>MMP</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - enzymology</subject><subject>Postmenopause</subject><subject>Progesterone - pharmacology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Surgery</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><subject>Up-Regulation</subject><subject>vascular remodeling</subject><subject>VSMC</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNp9ksGKFDEQhhtR3NnVB_Aiueit20qn00kQhGXY3RF2EFwFbyGTrmjG7mRNusV9ezPMoODBUwj5qvLzVVXVCwoNBdq_2Tf7nJsWQDbAGgD2qFpRULyWvWCPqxVA29adhO6sOs95D-WuBHtanVHJBSgmVpW9cg7tTKIjm5imGDCTGMjWzMn_IluczTjG-xRn9MHk8niDAclH_LqMZvaF9IFslskEchnT7C25m2Kcv5Htku2IZI3jmJ9VT5wZMz4_nRfV5-urT-tNffvh5v368ra2jNO5Vj0VQC30RqGkonXUAbc7J6ThwIaB9zuJg6KUC2OV4nwA00vletfDYGHHLqrXx74l748F86wnn21JYALGJetetR1XkhWQHkGbYs4Jnb5PfjLpQVPQB7N6r4tZfTCrgelittS8PDVfdhMOfytOKgvw6gSYbM3okgnW5z9cC52AroXCvT1yWFT89Jh0th6DxcGnMgk9RP_fGO_-qbajD758-B0fMO_jkkJxrKnOrQZ9d1iBwwaABKBSfGG_AT12qxw</recordid><startdate>200807</startdate><enddate>200807</enddate><creator>Grandas, Oscar H., M.D</creator><creator>Mountain, Deidra J.H., Ph.D</creator><creator>Kirkpatrick, Stacy S., B.S</creator><creator>Rudrapatna, Vivek S., M.D</creator><creator>Cassada, David C., M.D</creator><creator>Stevens, Scott L., M.D</creator><creator>Freeman, Michael B., M.D</creator><creator>Goldman, Mitchell H., M.D</creator><general>Elsevier Inc</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>200807</creationdate><title>Effect of Hormones on Matrix Metalloproteinases Gene Regulation in Human Aortic Smooth Muscle Cells</title><author>Grandas, Oscar H., M.D ; Mountain, Deidra J.H., Ph.D ; Kirkpatrick, Stacy S., B.S ; Rudrapatna, Vivek S., M.D ; Cassada, David C., M.D ; Stevens, Scott L., M.D ; Freeman, Michael B., M.D ; Goldman, Mitchell H., M.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c351t-961701c06a9e8172f1f05cbf78a503dd56b8ed91157ac9955d0a689f6f60dc0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell Culture Techniques</topic><topic>estrogen</topic><topic>Estrogens - pharmacology</topic><topic>Female</topic><topic>Gene Expression - drug effects</topic><topic>General aspects</topic><topic>HRT</topic><topic>Humans</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Matrix Metalloproteinase 14 - metabolism</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 3 - metabolism</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Medical sciences</topic><topic>MMP</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - enzymology</topic><topic>Postmenopause</topic><topic>Progesterone - pharmacology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Surgery</topic><topic>Tissue Inhibitor of Metalloproteinases - metabolism</topic><topic>Up-Regulation</topic><topic>vascular remodeling</topic><topic>VSMC</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grandas, Oscar H., M.D</creatorcontrib><creatorcontrib>Mountain, Deidra J.H., Ph.D</creatorcontrib><creatorcontrib>Kirkpatrick, Stacy S., B.S</creatorcontrib><creatorcontrib>Rudrapatna, Vivek S., M.D</creatorcontrib><creatorcontrib>Cassada, David C., M.D</creatorcontrib><creatorcontrib>Stevens, Scott L., M.D</creatorcontrib><creatorcontrib>Freeman, Michael B., M.D</creatorcontrib><creatorcontrib>Goldman, Mitchell H., M.D</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>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grandas, Oscar H., M.D</au><au>Mountain, Deidra J.H., Ph.D</au><au>Kirkpatrick, Stacy S., B.S</au><au>Rudrapatna, Vivek S., M.D</au><au>Cassada, David C., M.D</au><au>Stevens, Scott L., M.D</au><au>Freeman, Michael B., M.D</au><au>Goldman, Mitchell H., M.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Hormones on Matrix Metalloproteinases Gene Regulation in Human Aortic Smooth Muscle Cells</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2008-07</date><risdate>2008</risdate><volume>148</volume><issue>1</issue><spage>94</spage><epage>99</epage><pages>94-99</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><coden>JSGRA2</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Background Postmenopausal women receiving hormone replacement therapy have more adverse outcomes after vascular reconstructions. Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key group of enzymes involved in vascular remodeling are matrix metalloproteinases (MMPs). Here we studied the effect of estrogen (Est) and progesterone (Prog) on MMP gene expression in human VSMCs. Methods and results VSMCs were incubated with Est (5 ng/mL), Prog (50 ng/mL), Est+Prog combination (Est/Prog), and interleukin-1β (100 U/mL; IL-1β). Gene array analysis indicated Est+IL-1β increased the expression of MMP-3. Reverse transcriptase-polymer chain reaction (RT-PCR) analyses revealed MMP-3 mRNA levels were significantly increased by Est/Prog+IL-1β treatment. However, Western blot and further RT-PCR analyses indicated no change in MMP-3 in response to hormones alone. RT-PCR analyses revealed membrane type 1 (MT1)-MMP mRNA levels, not MMP-2 or tissue inhibitor of MMP (TIMP), were significantly increased by Est/Prog+IL-1β, and Western blot analyses confirmed a significant increase in MT1-MMP protein in response to Est alone. Conclusion Estrogen and progesterone affect the MMP pathway of VSMCs via isoform specific mechanisms and may lead to unbalanced MMP regulation. Estrogen up-regulates MT1-MMP without a corresponding increase in TIMP-2, known activator and inhibitor of MMP-2, respectively. Additionally, estrogen up-regulates MMP-3 only in the presence of IL-1β. This differential regulation, combined with case-specific variations in degree of inflammatory response, may explain why some women receiving exogenous hormone therapy at the time of vascular interventions are more susceptible to complications.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18570937</pmid><doi>10.1016/j.jss.2008.03.003</doi><tpages>6</tpages></addata></record> |
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| subjects | Biological and medical sciences Blotting, Western Cell Culture Techniques estrogen Estrogens - pharmacology Female Gene Expression - drug effects General aspects HRT Humans Interleukin-1beta - pharmacology Matrix Metalloproteinase 14 - metabolism Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 3 - metabolism Matrix Metalloproteinases - metabolism Medical sciences MMP Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - enzymology Postmenopause Progesterone - pharmacology Reverse Transcriptase Polymerase Chain Reaction Surgery Tissue Inhibitor of Metalloproteinases - metabolism Up-Regulation vascular remodeling VSMC |
| title | Effect of Hormones on Matrix Metalloproteinases Gene Regulation in Human Aortic Smooth Muscle Cells |
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