Morphological and Physiological Restorations of Hereditary Form of Dilated Cardiomyopathy by Somatic Gene Therapy
TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of δ-sarcoglycan (SG) and no expression of α-, β-, γ-, and δ-SG proteins are useful for developing the potential gene therapy of intractable heart failure. We prepared recombinant adeno-associated virus vector including normal δ-SG gene...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2001-06, Vol.284 (2), p.431-435 |
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| creator | Kawada, Tomie Sakamoto, Aiji Nakazawa, Mikio Urabe, Masashi Masuda, Fujiko Hemmi, Chieko Wang, Yue Soo Shin, Wee Nakatsuru, Yoko Sato, Hiroshi Ozawa, Keiya Toyo-oka, Teruhiko |
| description | TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of δ-sarcoglycan (SG) and no expression of α-, β-, γ-, and δ-SG proteins are useful for developing the potential gene therapy of intractable heart failure. We prepared recombinant adeno-associated virus vector including normal δ-SG gene driven by CMV promoter and intramurally administered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. Immunostaining demonstrated reexpression of not only δ-SG but also other three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferential amelioration of the diastolic indices (LVEDP, the dP/dtmin and CVP). These results provide the first evidence that supplementation of a specific gene with efficient and sustained transfection capability restores the genetic, morphological, and functional deteriorations. |
| doi_str_mv | 10.1006/bbrc.2001.4962 |
| format | Article |
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We prepared recombinant adeno-associated virus vector including normal δ-SG gene driven by CMV promoter and intramurally administered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. Immunostaining demonstrated reexpression of not only δ-SG but also other three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferential amelioration of the diastolic indices (LVEDP, the dP/dtmin and CVP). These results provide the first evidence that supplementation of a specific gene with efficient and sustained transfection capability restores the genetic, morphological, and functional deteriorations.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.2001.4962</identifier><identifier>PMID: 11394897</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adeno-associated virus ; Animals ; beta-Galactosidase - biosynthesis ; beta-Galactosidase - genetics ; cardiomyopathy ; Cardiomyopathy, Dilated - genetics ; Cardiomyopathy, Dilated - pathology ; Cardiomyopathy, Dilated - therapy ; Cell Size - drug effects ; Cricetinae ; Cytomegalovirus ; Cytoskeletal Proteins - administration & dosage ; Cytoskeletal Proteins - deficiency ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; d-sarcoglycan ; Dependovirus - genetics ; Disease Models, Animal ; Dystrophin - metabolism ; Gene Expression - drug effects ; gene therapy ; Genes, Reporter ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Genetic Vectors - genetics ; Genetic Vectors - metabolism ; Heart - drug effects ; heart failure ; hemodynamics ; Hemodynamics - drug effects ; Injections - methods ; Male ; Membrane Glycoproteins - administration & dosage ; Membrane Glycoproteins - deficiency ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Myocardium - metabolism ; Myocardium - pathology ; Sarcoglycans ; Transfection ; Treatment Outcome</subject><ispartof>Biochemical and biophysical research communications, 2001-06, Vol.284 (2), p.431-435</ispartof><rights>2001 Academic Press</rights><rights>Copyright 2001 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-67ffc29476d8e011baabeb97e75cfadaf7e120f5946f83d019c066d8a7ec4123</citedby><cites>FETCH-LOGICAL-c437t-67ffc29476d8e011baabeb97e75cfadaf7e120f5946f83d019c066d8a7ec4123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X01949629$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11394897$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawada, Tomie</creatorcontrib><creatorcontrib>Sakamoto, Aiji</creatorcontrib><creatorcontrib>Nakazawa, Mikio</creatorcontrib><creatorcontrib>Urabe, Masashi</creatorcontrib><creatorcontrib>Masuda, Fujiko</creatorcontrib><creatorcontrib>Hemmi, Chieko</creatorcontrib><creatorcontrib>Wang, Yue</creatorcontrib><creatorcontrib>Soo Shin, Wee</creatorcontrib><creatorcontrib>Nakatsuru, Yoko</creatorcontrib><creatorcontrib>Sato, Hiroshi</creatorcontrib><creatorcontrib>Ozawa, Keiya</creatorcontrib><creatorcontrib>Toyo-oka, Teruhiko</creatorcontrib><title>Morphological and Physiological Restorations of Hereditary Form of Dilated Cardiomyopathy by Somatic Gene Therapy</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of δ-sarcoglycan (SG) and no expression of α-, β-, γ-, and δ-SG proteins are useful for developing the potential gene therapy of intractable heart failure. We prepared recombinant adeno-associated virus vector including normal δ-SG gene driven by CMV promoter and intramurally administered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. Immunostaining demonstrated reexpression of not only δ-SG but also other three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferential amelioration of the diastolic indices (LVEDP, the dP/dtmin and CVP). These results provide the first evidence that supplementation of a specific gene with efficient and sustained transfection capability restores the genetic, morphological, and functional deteriorations.</description><subject>Adeno-associated virus</subject><subject>Animals</subject><subject>beta-Galactosidase - biosynthesis</subject><subject>beta-Galactosidase - genetics</subject><subject>cardiomyopathy</subject><subject>Cardiomyopathy, Dilated - genetics</subject><subject>Cardiomyopathy, Dilated - pathology</subject><subject>Cardiomyopathy, Dilated - therapy</subject><subject>Cell Size - drug effects</subject><subject>Cricetinae</subject><subject>Cytomegalovirus</subject><subject>Cytoskeletal Proteins - administration & dosage</subject><subject>Cytoskeletal Proteins - deficiency</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>d-sarcoglycan</subject><subject>Dependovirus - genetics</subject><subject>Disease Models, Animal</subject><subject>Dystrophin - metabolism</subject><subject>Gene Expression - drug effects</subject><subject>gene therapy</subject><subject>Genes, Reporter</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Genetic Vectors - genetics</subject><subject>Genetic Vectors - metabolism</subject><subject>Heart - drug effects</subject><subject>heart failure</subject><subject>hemodynamics</subject><subject>Hemodynamics - drug effects</subject><subject>Injections - methods</subject><subject>Male</subject><subject>Membrane Glycoproteins - administration & dosage</subject><subject>Membrane Glycoproteins - deficiency</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Sarcoglycans</subject><subject>Transfection</subject><subject>Treatment Outcome</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9LwzAYhoMoOn9cPUpO3jqTtmuao0ynwkTRHbyFNPniIm1Tk07of2_Khp7EU-Dj-V6-PC9C55RMKSHFVVV5NU0JodOcF-kemlDCSZJSku-jCYlEknL6doSOQ_iIFM0LfoiOKM14XnI2QZ-PzndrV7t3q2SNZavx83oI9mfyAqF3XvbWtQE7g-_Bg7a99ANeON-Moxtbyx40nkuvrWsG18l-PeBqwK-uiZsK30ELeLUGL7vhFB0YWQc4270naLW4Xc3vk-XT3cP8epmoPGN9UjBjVMpzVugS4uGVlBVUnAGbKSO1NAxoSsyM54UpM00oV6SIrGSgcppmJ-hyG9t597mJnxCNDQrqWrbgNkGw6CnLCP8XpKwsC57SCE63oPIuBA9GdN42UYSgRIxliLEMMZYhxjLiwsUueVM1oH_xnf0IlFsAoocvC14EZaFVUbAH1Qvt7F_Z35HYms4</recordid><startdate>20010608</startdate><enddate>20010608</enddate><creator>Kawada, Tomie</creator><creator>Sakamoto, Aiji</creator><creator>Nakazawa, Mikio</creator><creator>Urabe, Masashi</creator><creator>Masuda, Fujiko</creator><creator>Hemmi, Chieko</creator><creator>Wang, Yue</creator><creator>Soo Shin, Wee</creator><creator>Nakatsuru, Yoko</creator><creator>Sato, Hiroshi</creator><creator>Ozawa, Keiya</creator><creator>Toyo-oka, Teruhiko</creator><general>Elsevier Inc</general><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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20010608</creationdate><title>Morphological and Physiological Restorations of Hereditary Form of Dilated Cardiomyopathy by Somatic Gene Therapy</title><author>Kawada, Tomie ; Sakamoto, Aiji ; Nakazawa, Mikio ; Urabe, Masashi ; Masuda, Fujiko ; Hemmi, Chieko ; Wang, Yue ; Soo Shin, Wee ; Nakatsuru, Yoko ; Sato, Hiroshi ; Ozawa, Keiya ; Toyo-oka, Teruhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-67ffc29476d8e011baabeb97e75cfadaf7e120f5946f83d019c066d8a7ec4123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adeno-associated virus</topic><topic>Animals</topic><topic>beta-Galactosidase - biosynthesis</topic><topic>beta-Galactosidase - genetics</topic><topic>cardiomyopathy</topic><topic>Cardiomyopathy, Dilated - genetics</topic><topic>Cardiomyopathy, Dilated - pathology</topic><topic>Cardiomyopathy, Dilated - therapy</topic><topic>Cell Size - drug effects</topic><topic>Cricetinae</topic><topic>Cytomegalovirus</topic><topic>Cytoskeletal Proteins - administration & dosage</topic><topic>Cytoskeletal Proteins - deficiency</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>d-sarcoglycan</topic><topic>Dependovirus - genetics</topic><topic>Disease Models, Animal</topic><topic>Dystrophin - metabolism</topic><topic>Gene Expression - drug effects</topic><topic>gene therapy</topic><topic>Genes, Reporter</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Genetic Vectors - genetics</topic><topic>Genetic Vectors - metabolism</topic><topic>Heart - drug effects</topic><topic>heart failure</topic><topic>hemodynamics</topic><topic>Hemodynamics - drug effects</topic><topic>Injections - methods</topic><topic>Male</topic><topic>Membrane Glycoproteins - administration & dosage</topic><topic>Membrane Glycoproteins - deficiency</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Sarcoglycans</topic><topic>Transfection</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawada, Tomie</creatorcontrib><creatorcontrib>Sakamoto, Aiji</creatorcontrib><creatorcontrib>Nakazawa, Mikio</creatorcontrib><creatorcontrib>Urabe, Masashi</creatorcontrib><creatorcontrib>Masuda, Fujiko</creatorcontrib><creatorcontrib>Hemmi, Chieko</creatorcontrib><creatorcontrib>Wang, Yue</creatorcontrib><creatorcontrib>Soo Shin, Wee</creatorcontrib><creatorcontrib>Nakatsuru, Yoko</creatorcontrib><creatorcontrib>Sato, Hiroshi</creatorcontrib><creatorcontrib>Ozawa, Keiya</creatorcontrib><creatorcontrib>Toyo-oka, Teruhiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawada, Tomie</au><au>Sakamoto, Aiji</au><au>Nakazawa, Mikio</au><au>Urabe, Masashi</au><au>Masuda, Fujiko</au><au>Hemmi, Chieko</au><au>Wang, Yue</au><au>Soo Shin, Wee</au><au>Nakatsuru, Yoko</au><au>Sato, Hiroshi</au><au>Ozawa, Keiya</au><au>Toyo-oka, Teruhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morphological and Physiological Restorations of Hereditary Form of Dilated Cardiomyopathy by Somatic Gene Therapy</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2001-06-08</date><risdate>2001</risdate><volume>284</volume><issue>2</issue><spage>431</spage><epage>435</epage><pages>431-435</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of δ-sarcoglycan (SG) and no expression of α-, β-, γ-, and δ-SG proteins are useful for developing the potential gene therapy of intractable heart failure. We prepared recombinant adeno-associated virus vector including normal δ-SG gene driven by CMV promoter and intramurally administered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. Immunostaining demonstrated reexpression of not only δ-SG but also other three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferential amelioration of the diastolic indices (LVEDP, the dP/dtmin and CVP). These results provide the first evidence that supplementation of a specific gene with efficient and sustained transfection capability restores the genetic, morphological, and functional deteriorations.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11394897</pmid><doi>10.1006/bbrc.2001.4962</doi><tpages>5</tpages></addata></record> |
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| subjects | Adeno-associated virus Animals beta-Galactosidase - biosynthesis beta-Galactosidase - genetics cardiomyopathy Cardiomyopathy, Dilated - genetics Cardiomyopathy, Dilated - pathology Cardiomyopathy, Dilated - therapy Cell Size - drug effects Cricetinae Cytomegalovirus Cytoskeletal Proteins - administration & dosage Cytoskeletal Proteins - deficiency Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism d-sarcoglycan Dependovirus - genetics Disease Models, Animal Dystrophin - metabolism Gene Expression - drug effects gene therapy Genes, Reporter Genetic Therapy - methods Genetic Vectors - administration & dosage Genetic Vectors - genetics Genetic Vectors - metabolism Heart - drug effects heart failure hemodynamics Hemodynamics - drug effects Injections - methods Male Membrane Glycoproteins - administration & dosage Membrane Glycoproteins - deficiency Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Myocardium - metabolism Myocardium - pathology Sarcoglycans Transfection Treatment Outcome |
| title | Morphological and Physiological Restorations of Hereditary Form of Dilated Cardiomyopathy by Somatic Gene Therapy |
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