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Adenovirus-mediated delivery of Fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals
Adenoviral constructs have been used for studies of injury-induced vascular hyperplasia in immunologically naive laboratory animals, but their usefulness for intra-arterial gene therapy may be limited by the prevalence of preexisting immunity to adenovirus in the patient population. Here, we explore...
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| Published in: | Circulation (New York, N.Y.) N.Y.), 1999-04, Vol.99 (14), p.1776-1779 |
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| container_end_page | 1779 |
| container_issue | 14 |
| container_start_page | 1776 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 99 |
| creator | ZHENGYU LUO SATA, M THAO NGUYEN KAPLAN, J. M AKITA, G. Y WALSH, K |
| description | Adenoviral constructs have been used for studies of injury-induced vascular hyperplasia in immunologically naive laboratory animals, but their usefulness for intra-arterial gene therapy may be limited by the prevalence of preexisting immunity to adenovirus in the patient population. Here, we explored the efficacy of adenovirus-mediated transfer of Fas ligand, a cytotoxic gene with immunomodulatory properties, in inhibiting injury-induced vascular lesion formation in both naive and immunologically primed animals.
Lesion formation was evaluated in balloon-injured carotid arteries of naive and adenovirus-immunized rats that were infected with adenoviral constructs expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad-p21), or beta-galactosidase (Ad-betagal). In naive rats, Ad-FasL induced apoptosis in medial vascular smooth muscle cells and inhibited intimal hyperplasia by 60% relative to Ad-betagal-treated vessels (P |
| doi_str_mv | 10.1161/01.cir.99.14.1776 |
| format | article |
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Lesion formation was evaluated in balloon-injured carotid arteries of naive and adenovirus-immunized rats that were infected with adenoviral constructs expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad-p21), or beta-galactosidase (Ad-betagal). In naive rats, Ad-FasL induced apoptosis in medial vascular smooth muscle cells and inhibited intimal hyperplasia by 60% relative to Ad-betagal-treated vessels (P<0.05), whereas the cytostatic agent Ad-p21 decreased lesion size by 58% (P<0.05). In animals preimmunized with an adenoviral vector containing no transgene, Ad-FasL significantly inhibited neointima formation (73% reduction, P<0.05), but Ad-p21 failed to inhibit neointima formation relative to controls. Immunologically primed rats displayed robust T-cell infiltration in Ad-p21- and Ad-betagal-treated vessels, but T-cell infiltration was markedly attenuated in Ad-FasL-treated vessels.
Our data demonstrate that adenovirus-mediated Fas ligand delivery can inhibit intimal hyperplasia in both immunologically primed and naive animals, whereas the efficacy of an adenovirus-mediated p21 delivery is limited to immunologically naive animals. This study documents, for the first time, the therapeutic efficacy of intravascular adenoviral gene transfer in animals with preexisting immunity to adenovirus.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.99.14.1776</identifier><identifier>PMID: 10199871</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adenoviridae - genetics ; Adenoviridae - immunology ; Animals ; Biological and medical sciences ; Carotid Arteries - drug effects ; Carotid Arteries - pathology ; Carotid Artery Diseases - pathology ; Carotid Artery Diseases - prevention & control ; Catheterization ; Diseases of the cardiovascular system ; Fas Ligand Protein ; Gene Transfer Techniques ; Hyperplasia - prevention & control ; Immunization ; Male ; Medical sciences ; Membrane Glycoproteins - administration & dosage ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - pharmacology ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Rats ; Rats, Sprague-Dawley ; Tunica Intima - pathology ; Vasculitis - prevention & control</subject><ispartof>Circulation (New York, N.Y.), 1999-04, Vol.99 (14), p.1776-1779</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Apr 13, 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-c7472d5b027b23a5212720996a624d63714fddd1058e5df41e13baed15d638953</citedby><cites>FETCH-LOGICAL-c504t-c7472d5b027b23a5212720996a624d63714fddd1058e5df41e13baed15d638953</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=1743883$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10199871$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ZHENGYU LUO</creatorcontrib><creatorcontrib>SATA, M</creatorcontrib><creatorcontrib>THAO NGUYEN</creatorcontrib><creatorcontrib>KAPLAN, J. M</creatorcontrib><creatorcontrib>AKITA, G. Y</creatorcontrib><creatorcontrib>WALSH, K</creatorcontrib><title>Adenovirus-mediated delivery of Fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Adenoviral constructs have been used for studies of injury-induced vascular hyperplasia in immunologically naive laboratory animals, but their usefulness for intra-arterial gene therapy may be limited by the prevalence of preexisting immunity to adenovirus in the patient population. Here, we explored the efficacy of adenovirus-mediated transfer of Fas ligand, a cytotoxic gene with immunomodulatory properties, in inhibiting injury-induced vascular lesion formation in both naive and immunologically primed animals.
Lesion formation was evaluated in balloon-injured carotid arteries of naive and adenovirus-immunized rats that were infected with adenoviral constructs expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad-p21), or beta-galactosidase (Ad-betagal). In naive rats, Ad-FasL induced apoptosis in medial vascular smooth muscle cells and inhibited intimal hyperplasia by 60% relative to Ad-betagal-treated vessels (P<0.05), whereas the cytostatic agent Ad-p21 decreased lesion size by 58% (P<0.05). In animals preimmunized with an adenoviral vector containing no transgene, Ad-FasL significantly inhibited neointima formation (73% reduction, P<0.05), but Ad-p21 failed to inhibit neointima formation relative to controls. Immunologically primed rats displayed robust T-cell infiltration in Ad-p21- and Ad-betagal-treated vessels, but T-cell infiltration was markedly attenuated in Ad-FasL-treated vessels.
Our data demonstrate that adenovirus-mediated Fas ligand delivery can inhibit intimal hyperplasia in both immunologically primed and naive animals, whereas the efficacy of an adenovirus-mediated p21 delivery is limited to immunologically naive animals. This study documents, for the first time, the therapeutic efficacy of intravascular adenoviral gene transfer in animals with preexisting immunity to adenovirus.</description><subject>Adenoviridae - genetics</subject><subject>Adenoviridae - immunology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carotid Arteries - drug effects</subject><subject>Carotid Arteries - pathology</subject><subject>Carotid Artery Diseases - pathology</subject><subject>Carotid Artery Diseases - prevention & control</subject><subject>Catheterization</subject><subject>Diseases of the cardiovascular system</subject><subject>Fas Ligand Protein</subject><subject>Gene Transfer Techniques</subject><subject>Hyperplasia - prevention & control</subject><subject>Immunization</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - administration & dosage</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - pharmacology</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>Tunica Intima - pathology</subject><subject>Vasculitis - prevention & control</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNpdkU2LFDEQhoMo7rj6A7xIEPHWbSqfneMyuLqwIIieQ7qT3s2Q7oxJ98Jc_O2mmQHFU1Wop95K1YvQWyAtgIRPBNoh5FbrFngLSslnaAeC8oYLpp-jHSFEN4pReoVelXKoT8mUeImugIDWnYId-n3j_JyeQl5LM3kX7OIddj6GJ59POI341hYcw4OdHQ7zY-jDUmqyhMlG_Hg6-nyMtgSL7bj4jHsbY0pzJQ5r7Q81m6Z1TjE9hKHWTviYQ52D7bwplNfoxViDf3OJ1-jn7ecf-6_N_bcvd_ub-2YQhC_NoLiiTvSEqp4yKyhQRYnW0krKXV0K-OicAyI6L9zIwQPrrXcgarHTgl2jj2fdY06_Vl8WM4Uy-Bjt7NNajNSyU4LrCr7_DzykNc_1b6YOlUqD3NTgDA05lZL9aLatbD4ZIGZzxhAw-7vvRmsD3GzO1J53F-G1rwf4p-NsRQU-XABb6qnGbOchlL-c4qzrGPsDffSYEg</recordid><startdate>19990413</startdate><enddate>19990413</enddate><creator>ZHENGYU LUO</creator><creator>SATA, M</creator><creator>THAO NGUYEN</creator><creator>KAPLAN, J. M</creator><creator>AKITA, G. Y</creator><creator>WALSH, K</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19990413</creationdate><title>Adenovirus-mediated delivery of Fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals</title><author>ZHENGYU LUO ; SATA, M ; THAO NGUYEN ; KAPLAN, J. M ; AKITA, G. Y ; WALSH, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-c7472d5b027b23a5212720996a624d63714fddd1058e5df41e13baed15d638953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenoviridae - immunology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carotid Arteries - drug effects</topic><topic>Carotid Arteries - pathology</topic><topic>Carotid Artery Diseases - pathology</topic><topic>Carotid Artery Diseases - prevention & control</topic><topic>Catheterization</topic><topic>Diseases of the cardiovascular system</topic><topic>Fas Ligand Protein</topic><topic>Gene Transfer Techniques</topic><topic>Hyperplasia - prevention & control</topic><topic>Immunization</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - administration & dosage</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - pharmacology</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>Tunica Intima - pathology</topic><topic>Vasculitis - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ZHENGYU LUO</creatorcontrib><creatorcontrib>SATA, M</creatorcontrib><creatorcontrib>THAO NGUYEN</creatorcontrib><creatorcontrib>KAPLAN, J. M</creatorcontrib><creatorcontrib>AKITA, G. 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Here, we explored the efficacy of adenovirus-mediated transfer of Fas ligand, a cytotoxic gene with immunomodulatory properties, in inhibiting injury-induced vascular lesion formation in both naive and immunologically primed animals.
Lesion formation was evaluated in balloon-injured carotid arteries of naive and adenovirus-immunized rats that were infected with adenoviral constructs expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad-p21), or beta-galactosidase (Ad-betagal). In naive rats, Ad-FasL induced apoptosis in medial vascular smooth muscle cells and inhibited intimal hyperplasia by 60% relative to Ad-betagal-treated vessels (P<0.05), whereas the cytostatic agent Ad-p21 decreased lesion size by 58% (P<0.05). In animals preimmunized with an adenoviral vector containing no transgene, Ad-FasL significantly inhibited neointima formation (73% reduction, P<0.05), but Ad-p21 failed to inhibit neointima formation relative to controls. Immunologically primed rats displayed robust T-cell infiltration in Ad-p21- and Ad-betagal-treated vessels, but T-cell infiltration was markedly attenuated in Ad-FasL-treated vessels.
Our data demonstrate that adenovirus-mediated Fas ligand delivery can inhibit intimal hyperplasia in both immunologically primed and naive animals, whereas the efficacy of an adenovirus-mediated p21 delivery is limited to immunologically naive animals. This study documents, for the first time, the therapeutic efficacy of intravascular adenoviral gene transfer in animals with preexisting immunity to adenovirus.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>10199871</pmid><doi>10.1161/01.cir.99.14.1776</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 1999-04, Vol.99 (14), p.1776-1779 |
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| subjects | Adenoviridae - genetics Adenoviridae - immunology Animals Biological and medical sciences Carotid Arteries - drug effects Carotid Arteries - pathology Carotid Artery Diseases - pathology Carotid Artery Diseases - prevention & control Catheterization Diseases of the cardiovascular system Fas Ligand Protein Gene Transfer Techniques Hyperplasia - prevention & control Immunization Male Medical sciences Membrane Glycoproteins - administration & dosage Membrane Glycoproteins - genetics Membrane Glycoproteins - pharmacology Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Rats Rats, Sprague-Dawley Tunica Intima - pathology Vasculitis - prevention & control |
| title | Adenovirus-mediated delivery of Fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals |
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