Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats
Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the...
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| Veröffentlicht in: | Stroke (1970) 2007, Vol.38 (1), p.162-169 |
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| creator | AOKI, Tomohiro KATAOKA, Hiroharu MORIMOTO, Masafumi NOZAKI, Kazuhiko HASHIMOTO, Nobuo |
| description | Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the significance of MMPs in the progression of cerebral aneurysms.
Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9.
Macrophages infiltrated in arterial walls of experimentally induced rat cerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of rat cerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model.
These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease. |
| doi_str_mv | 10.1161/01.STR.0000252129.18605.c8 |
| format | Article |
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Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9.
Macrophages infiltrated in arterial walls of experimentally induced rat cerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of rat cerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model.
These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/01.STR.0000252129.18605.c8</identifier><identifier>PMID: 17122420</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Cerebral Arteries - enzymology ; Cerebral Arteries - physiopathology ; Chemotaxis, Leukocyte - drug effects ; Chemotaxis, Leukocyte - physiology ; Disease Models, Animal ; Disease Progression ; Diseases of the nervous system ; Enzyme Inhibitors - pharmacology ; Immunohistochemistry ; Intracranial Aneurysm - enzymology ; Intracranial Aneurysm - physiopathology ; Macrophages - drug effects ; Macrophages - enzymology ; Macrophages - secretion ; Male ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 2 - secretion ; Matrix Metalloproteinase 9 - metabolism ; Matrix Metalloproteinase 9 - secretion ; Matrix Metalloproteinase Inhibitors ; Medical sciences ; Neurology ; Neuropharmacology ; Neuroprotective agent ; Pharmacology. Drug treatments ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular diseases and vascular malformations of the nervous system ; Vasculitis - enzymology ; Vasculitis - physiopathology</subject><ispartof>Stroke (1970), 2007, Vol.38 (1), p.162-169</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c683t-fb92a1cd8aa32afbca9961db385bc02169656ab240f41c1df9c84ad7289df1ca3</citedby><cites>FETCH-LOGICAL-c683t-fb92a1cd8aa32afbca9961db385bc02169656ab240f41c1df9c84ad7289df1ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18430067$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17122420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>AOKI, Tomohiro</creatorcontrib><creatorcontrib>KATAOKA, Hiroharu</creatorcontrib><creatorcontrib>MORIMOTO, Masafumi</creatorcontrib><creatorcontrib>NOZAKI, Kazuhiko</creatorcontrib><creatorcontrib>HASHIMOTO, Nobuo</creatorcontrib><title>Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the significance of MMPs in the progression of cerebral aneurysms.
Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9.
Macrophages infiltrated in arterial walls of experimentally induced rat cerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of rat cerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model.
These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cerebral Arteries - enzymology</subject><subject>Cerebral Arteries - physiopathology</subject><subject>Chemotaxis, Leukocyte - drug effects</subject><subject>Chemotaxis, Leukocyte - physiology</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Diseases of the nervous system</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Immunohistochemistry</subject><subject>Intracranial Aneurysm - enzymology</subject><subject>Intracranial Aneurysm - physiopathology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - enzymology</subject><subject>Macrophages - secretion</subject><subject>Male</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 2 - secretion</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix Metalloproteinase 9 - secretion</subject><subject>Matrix Metalloproteinase Inhibitors</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Pharmacology. Drug treatments</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Vasculitis - enzymology</subject><subject>Vasculitis - physiopathology</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rHDEMhk1paDZp_0IxgfY2E0sz47VzC6FtAimBdHs2Gn8kE-ZjY8-W7L-Pt1nYY3SREI-kF72MnYEoASScCyj_rO5LkQMbBNQlKCma0qoPbAEN1kUtUX1kCyEqXWCt9TE7Selpx1eq-cSOYQmINYoFe_pNNk7rR3rwhfOx--cdH2iO3Qsf_Ex9P63jNPtupOQL5DQ6Xmiee0Pu8vnR7-qH6FPqppFPgVsffRupz6jfxG0aEu9GHmlOn9lRoD75L_t8yv7-_LG6ui5u737dXF3eFlaqai5Cq5HAOkVUIYXWktYSXJuVt1YgSC0bSS3WItRgwQVtVU1uiUq7AJaqU_b9bW9W9rzxaTZDl6zv-6xo2iSTryhElO-CoPMvc2Tw4g3Mr0op-mDWsRsobg0Is7PECDDZEnOwxPy3xFiVh7_ur2zawbvD6N6DDHzbA5Qs9SHSaLt04FRdCSGX1SvQXZbp</recordid><startdate>2007</startdate><enddate>2007</enddate><creator>AOKI, Tomohiro</creator><creator>KATAOKA, Hiroharu</creator><creator>MORIMOTO, Masafumi</creator><creator>NOZAKI, Kazuhiko</creator><creator>HASHIMOTO, Nobuo</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>2007</creationdate><title>Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats</title><author>AOKI, Tomohiro ; KATAOKA, Hiroharu ; MORIMOTO, Masafumi ; NOZAKI, Kazuhiko ; HASHIMOTO, Nobuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c683t-fb92a1cd8aa32afbca9961db385bc02169656ab240f41c1df9c84ad7289df1ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cerebral Arteries - enzymology</topic><topic>Cerebral Arteries - physiopathology</topic><topic>Chemotaxis, Leukocyte - drug effects</topic><topic>Chemotaxis, Leukocyte - physiology</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Diseases of the nervous system</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Immunohistochemistry</topic><topic>Intracranial Aneurysm - enzymology</topic><topic>Intracranial Aneurysm - physiopathology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - enzymology</topic><topic>Macrophages - secretion</topic><topic>Male</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 2 - secretion</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix Metalloproteinase 9 - secretion</topic><topic>Matrix Metalloproteinase Inhibitors</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Pharmacology. Drug treatments</topic><topic>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Vasculitis - enzymology</topic><topic>Vasculitis - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>AOKI, Tomohiro</creatorcontrib><creatorcontrib>KATAOKA, Hiroharu</creatorcontrib><creatorcontrib>MORIMOTO, Masafumi</creatorcontrib><creatorcontrib>NOZAKI, Kazuhiko</creatorcontrib><creatorcontrib>HASHIMOTO, Nobuo</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>AOKI, Tomohiro</au><au>KATAOKA, Hiroharu</au><au>MORIMOTO, Masafumi</au><au>NOZAKI, Kazuhiko</au><au>HASHIMOTO, Nobuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2007</date><risdate>2007</risdate><volume>38</volume><issue>1</issue><spage>162</spage><epage>169</epage><pages>162-169</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>Mechanisms of initiation, progression and rupture of cerebral aneurysms have not yet been fully understood despite its clinical significance. Matrix metalloproteinases (MMPs) are a family of proteinases which are involved in the remodeling of vascular walls. In the present study, we investigated the significance of MMPs in the progression of cerebral aneurysms.
Cerebral aneurysms were experimentally induced in 7-week-old male Sprague-Dawley rats. MMP-2 and MMP-9 expression was examined by immunohistochemistry and RT-PCR. Gelatinase activity in aneurysmal walls was assessed by in situ zymography. A selective inhibitor for MMP-2, -9 and -12, tolylsam, was used to examine the effect of inhibition of MMP-2 and MMP-9.
Macrophages infiltrated in arterial walls of experimentally induced rat cerebral aneurysms and expressed MMP-2 and -9. Macrophage infiltration and MMP expression was increased with the progression of aneurysms. Gelatinase activity attributable to MMP-2 and MMP-9 increased in arterial walls of rat cerebral aneurysms. Furthermore, tolylsam reduced the ratio of advanced aneurysms in our rat model.
These data suggest that macrophage-derived MMP-2 and -9 may play an important role in the progression of cerebral aneurysms. The findings of this study will shed a new light into the pathogenesis of cerebral aneurysms and highlight the importance of inflammatory response causing the degeneration of extracellular matrix in the process of this disease.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>17122420</pmid><doi>10.1161/01.STR.0000252129.18605.c8</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Cerebral Arteries - enzymology Cerebral Arteries - physiopathology Chemotaxis, Leukocyte - drug effects Chemotaxis, Leukocyte - physiology Disease Models, Animal Disease Progression Diseases of the nervous system Enzyme Inhibitors - pharmacology Immunohistochemistry Intracranial Aneurysm - enzymology Intracranial Aneurysm - physiopathology Macrophages - drug effects Macrophages - enzymology Macrophages - secretion Male Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 2 - secretion Matrix Metalloproteinase 9 - metabolism Matrix Metalloproteinase 9 - secretion Matrix Metalloproteinase Inhibitors Medical sciences Neurology Neuropharmacology Neuroprotective agent Pharmacology. Drug treatments Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Vascular diseases and vascular malformations of the nervous system Vasculitis - enzymology Vasculitis - physiopathology |
| title | Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats |
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