Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes
Hemorrhagic conversion after tissue plasminogen activator (tPA) stroke therapy has been linked with elevations in matrix metalloproteinase-9 (MMP-9) at the neurovascular interface. Here, we test the idea that statins may directly ameliorate tPA-induced MMP-9 dysregulation. Recombinant human tPA (5 m...
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| Veröffentlicht in: | Stroke (1970) 2006-07, Vol.37 (7), p.1910-1912 |
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| container_title | Stroke (1970) |
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| creator | WANG, Sophia LEE, Sun-Ryung GUO, Shu-Zhen WOO JEAN KIM MONTANER, Joan XIAOYING WANG LO, Eng H |
| description | Hemorrhagic conversion after tissue plasminogen activator (tPA) stroke therapy has been linked with elevations in matrix metalloproteinase-9 (MMP-9) at the neurovascular interface. Here, we test the idea that statins may directly ameliorate tPA-induced MMP-9 dysregulation.
Recombinant human tPA (5 microg/mL) was added to primary rat cortical astrocytes. Zymography was used to quantify MMP-9 levels in conditioned media. Effects of simvastatin or the Rho kinase inhibitor Y-27632 were assessed by pretreating cells before tPA exposure.
Simvastatin (1 to 10 micromol/L) significantly reduced tPA-induced MMP-9 in cortical astrocytes. This effect may be mediated via the Rho kinase pathway because tPA-induced activation of Rho signaling was suppressed by simvastatin, and tPA-induced MMP-9 levels were similarly reduced by the Rho kinase inhibitor Y-27632 (1 to 10 micromol/L).
Statins reduce tPA-induced MMP-9 dysregulation by inhibiting the Rho signaling pathway. Statins may ameliorate tPA-associated MMP imbalances in stroke. |
| doi_str_mv | 10.1161/01.str.0000226923.48905.39 |
| format | Article |
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Recombinant human tPA (5 microg/mL) was added to primary rat cortical astrocytes. Zymography was used to quantify MMP-9 levels in conditioned media. Effects of simvastatin or the Rho kinase inhibitor Y-27632 were assessed by pretreating cells before tPA exposure.
Simvastatin (1 to 10 micromol/L) significantly reduced tPA-induced MMP-9 in cortical astrocytes. This effect may be mediated via the Rho kinase pathway because tPA-induced activation of Rho signaling was suppressed by simvastatin, and tPA-induced MMP-9 levels were similarly reduced by the Rho kinase inhibitor Y-27632 (1 to 10 micromol/L).
Statins reduce tPA-induced MMP-9 dysregulation by inhibiting the Rho signaling pathway. Statins may ameliorate tPA-associated MMP imbalances in stroke.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/01.str.0000226923.48905.39</identifier><identifier>PMID: 16741180</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Amides - pharmacology ; Animals ; Astrocytes - drug effects ; Astrocytes - enzymology ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Cells, Cultured - drug effects ; Cells, Cultured - enzymology ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; Cerebral Hemorrhage - etiology ; Drug Evaluation, Preclinical ; Enzyme Induction - drug effects ; Fundamental and applied biological sciences. Psychology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Intracellular Signaling Peptides and Proteins ; Matrix Metalloproteinase 2 - biosynthesis ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 9 - biosynthesis ; Matrix Metalloproteinase 9 - genetics ; Medical sciences ; Neurology ; Neuroprotective Agents - pharmacology ; Pharmacology. Drug treatments ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Pyridines - pharmacology ; Rats ; Recombinant Proteins - pharmacology ; rho-Associated Kinases ; Signal Transduction - drug effects ; Simvastatin - pharmacology ; Stroke - complications ; Stroke - enzymology ; Vascular diseases and vascular malformations of the nervous system ; Vertebrates: nervous system and sense organs</subject><ispartof>Stroke (1970), 2006-07, Vol.37 (7), p.1910-1912</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-6a38da2857db5236350fe6d3bdf30c5c27d94d8acee3029085bf631decba7a1b3</citedby><cites>FETCH-LOGICAL-c532t-6a38da2857db5236350fe6d3bdf30c5c27d94d8acee3029085bf631decba7a1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17920072$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16741180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WANG, Sophia</creatorcontrib><creatorcontrib>LEE, Sun-Ryung</creatorcontrib><creatorcontrib>GUO, Shu-Zhen</creatorcontrib><creatorcontrib>WOO JEAN KIM</creatorcontrib><creatorcontrib>MONTANER, Joan</creatorcontrib><creatorcontrib>XIAOYING WANG</creatorcontrib><creatorcontrib>LO, Eng H</creatorcontrib><title>Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>Hemorrhagic conversion after tissue plasminogen activator (tPA) stroke therapy has been linked with elevations in matrix metalloproteinase-9 (MMP-9) at the neurovascular interface. Here, we test the idea that statins may directly ameliorate tPA-induced MMP-9 dysregulation.
Recombinant human tPA (5 microg/mL) was added to primary rat cortical astrocytes. Zymography was used to quantify MMP-9 levels in conditioned media. Effects of simvastatin or the Rho kinase inhibitor Y-27632 were assessed by pretreating cells before tPA exposure.
Simvastatin (1 to 10 micromol/L) significantly reduced tPA-induced MMP-9 in cortical astrocytes. This effect may be mediated via the Rho kinase pathway because tPA-induced activation of Rho signaling was suppressed by simvastatin, and tPA-induced MMP-9 levels were similarly reduced by the Rho kinase inhibitor Y-27632 (1 to 10 micromol/L).
Statins reduce tPA-induced MMP-9 dysregulation by inhibiting the Rho signaling pathway. Statins may ameliorate tPA-associated MMP imbalances in stroke.</description><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - enzymology</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cells, Cultured - drug effects</subject><subject>Cells, Cultured - enzymology</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>Cerebral Hemorrhage - etiology</subject><subject>Drug Evaluation, Preclinical</subject><subject>Enzyme Induction - drug effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Matrix Metalloproteinase 2 - biosynthesis</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Matrix Metalloproteinase 9 - biosynthesis</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Pyridines - pharmacology</subject><subject>Rats</subject><subject>Recombinant Proteins - pharmacology</subject><subject>rho-Associated Kinases</subject><subject>Signal Transduction - drug effects</subject><subject>Simvastatin - pharmacology</subject><subject>Stroke - complications</subject><subject>Stroke - enzymology</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1r3TAMhs1YWc-6_YURBttdUn_Ejr27UfYFhUHbXRvFVoZHEp_ZTun593XXA-dyQiCBnlcSvIS8Z7RjTLFLyrpcUkdrcK4MF12vDZWdMC_Ijknet73i-iXZUSpMy3tjzsnrnP888ULLV-ScqaFnTNMdCTfoN1dCXJs4NSXkvGGznyEvYY2_cW2gDu-hxNSGtZLomwVKCg_NggXmOe5TLBhWyNiaZjw0OSz3kAuUsDY1a5uiOxTMb8jZBHPGt8d6QX59_XJ39b29_vntx9Xn69ZJwUurQGgPXMvBj5ILJSSdUHkx-klQJx0fvOm9BocoKDdUy3FSgnl0IwzARnFBPj7vrZ_93TAXu4TscJ5hxbhlq7TUikv1X5ANXKlB6Qp-egZdijknnOw-hQXSwTJqnxyxlNnbuxt7csT-c8QKU8Xvjle2cUF_kh4tqMCHIwDZwTwlWF3IJ24wnNKBi0ciEpfK</recordid><startdate>20060701</startdate><enddate>20060701</enddate><creator>WANG, Sophia</creator><creator>LEE, Sun-Ryung</creator><creator>GUO, Shu-Zhen</creator><creator>WOO JEAN KIM</creator><creator>MONTANER, Joan</creator><creator>XIAOYING WANG</creator><creator>LO, Eng H</creator><general>Lippincott Williams & Wilkins</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20060701</creationdate><title>Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes</title><author>WANG, Sophia ; LEE, Sun-Ryung ; GUO, Shu-Zhen ; WOO JEAN KIM ; MONTANER, Joan ; XIAOYING WANG ; LO, Eng H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-6a38da2857db5236350fe6d3bdf30c5c27d94d8acee3029085bf631decba7a1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - enzymology</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cells, Cultured - drug effects</topic><topic>Cells, Cultured - enzymology</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>Cerebral Hemorrhage - etiology</topic><topic>Drug Evaluation, Preclinical</topic><topic>Enzyme Induction - drug effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Matrix Metalloproteinase 2 - biosynthesis</topic><topic>Matrix Metalloproteinase 2 - genetics</topic><topic>Matrix Metalloproteinase 9 - biosynthesis</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Pyridines - pharmacology</topic><topic>Rats</topic><topic>Recombinant Proteins - pharmacology</topic><topic>rho-Associated Kinases</topic><topic>Signal Transduction - drug effects</topic><topic>Simvastatin - pharmacology</topic><topic>Stroke - complications</topic><topic>Stroke - enzymology</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WANG, Sophia</creatorcontrib><creatorcontrib>LEE, Sun-Ryung</creatorcontrib><creatorcontrib>GUO, Shu-Zhen</creatorcontrib><creatorcontrib>WOO JEAN KIM</creatorcontrib><creatorcontrib>MONTANER, Joan</creatorcontrib><creatorcontrib>XIAOYING WANG</creatorcontrib><creatorcontrib>LO, Eng H</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WANG, Sophia</au><au>LEE, Sun-Ryung</au><au>GUO, Shu-Zhen</au><au>WOO JEAN KIM</au><au>MONTANER, Joan</au><au>XIAOYING WANG</au><au>LO, Eng H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2006-07-01</date><risdate>2006</risdate><volume>37</volume><issue>7</issue><spage>1910</spage><epage>1912</epage><pages>1910-1912</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>Hemorrhagic conversion after tissue plasminogen activator (tPA) stroke therapy has been linked with elevations in matrix metalloproteinase-9 (MMP-9) at the neurovascular interface. Here, we test the idea that statins may directly ameliorate tPA-induced MMP-9 dysregulation.
Recombinant human tPA (5 microg/mL) was added to primary rat cortical astrocytes. Zymography was used to quantify MMP-9 levels in conditioned media. Effects of simvastatin or the Rho kinase inhibitor Y-27632 were assessed by pretreating cells before tPA exposure.
Simvastatin (1 to 10 micromol/L) significantly reduced tPA-induced MMP-9 in cortical astrocytes. This effect may be mediated via the Rho kinase pathway because tPA-induced activation of Rho signaling was suppressed by simvastatin, and tPA-induced MMP-9 levels were similarly reduced by the Rho kinase inhibitor Y-27632 (1 to 10 micromol/L).
Statins reduce tPA-induced MMP-9 dysregulation by inhibiting the Rho signaling pathway. Statins may ameliorate tPA-associated MMP imbalances in stroke.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>16741180</pmid><doi>10.1161/01.str.0000226923.48905.39</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0039-2499 1524-4628 |
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| source | MEDLINE; American Heart Association; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amides - pharmacology Animals Astrocytes - drug effects Astrocytes - enzymology Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Cells, Cultured - drug effects Cells, Cultured - enzymology Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Cerebral Hemorrhage - etiology Drug Evaluation, Preclinical Enzyme Induction - drug effects Fundamental and applied biological sciences. Psychology Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Intracellular Signaling Peptides and Proteins Matrix Metalloproteinase 2 - biosynthesis Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 9 - biosynthesis Matrix Metalloproteinase 9 - genetics Medical sciences Neurology Neuroprotective Agents - pharmacology Pharmacology. Drug treatments Protein-Serine-Threonine Kinases - antagonists & inhibitors Pyridines - pharmacology Rats Recombinant Proteins - pharmacology rho-Associated Kinases Signal Transduction - drug effects Simvastatin - pharmacology Stroke - complications Stroke - enzymology Vascular diseases and vascular malformations of the nervous system Vertebrates: nervous system and sense organs |
| title | Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes |
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