Adenovirus-mediated gene transfer of soluble vascular cell adhesion molecule to porcine interposition vein grafts

The efficacy of aorto-coronary vein grafting is limited by early graft thrombosis and accelerated graft atherosclerosis. Direct adenovirus-mediated transfer of genes encoding inhibitory proteins may prevent or slow progression of vein graft disease. Recombinant adenoviruses containing the cDNA for t...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 1994-05, Vol.89 (5), p.1922-1928
Hauptverfasser: SHI-JEN CHEN, WILSON, J. M, MULLER, D. W. M
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container_end_page 1928
container_issue 5
container_start_page 1922
container_title Circulation (New York, N.Y.)
container_volume 89
creator SHI-JEN CHEN
WILSON, J. M
MULLER, D. W. M
description The efficacy of aorto-coronary vein grafting is limited by early graft thrombosis and accelerated graft atherosclerosis. Direct adenovirus-mediated transfer of genes encoding inhibitory proteins may prevent or slow progression of vein graft disease. Recombinant adenoviruses containing the cDNA for the marker gene lacZ (Ad.CMVlacZ) or soluble vascular cell adhesion molecule (sVCAM) (Ad.CB-sVCAM) were used to infect segments of porcine jugular vein or human saphenous vein. Ex vivo testing showed expression of the introduced genes after incubation with Ad.CMVlacZ or Ad.CBsVCAM for periods from 1 to 24 hours, with an increase in transfection efficiency with increasing incubation time. Porcine jugular veins were then interposed as vascular grafts in the carotid arteries of four juvenile farm pigs after ex vivo gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or Ad.CBsVCAM. sVCAM-transfected carotid vein grafts were placed on one side and lacZ transfected veins were placed contralaterally as controls. Three days later, the vein graft segments were resected. Expression of the lacZ gene was confirmed by X-Gal chromagen staining and visualization by light and transmission electron microscopy. Gene expression was apparent in all layers of the vein graft wall, with prominent staining in the adventitia. sVCAM expression was confirmed by immunohistochemistry and in situ hybridization. We conclude that ex vivo gene transfer before vein grafting is feasible using a replication-deficient recombinant adenovirus and results in a high level of gene expression in vivo. The potential for this approach to prevent early vein graft thrombosis or accelerated vein graft atherosclerosis requires further evaluation.
doi_str_mv 10.1161/01.CIR.89.5.1922
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Porcine jugular veins were then interposed as vascular grafts in the carotid arteries of four juvenile farm pigs after ex vivo gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or Ad.CBsVCAM. sVCAM-transfected carotid vein grafts were placed on one side and lacZ transfected veins were placed contralaterally as controls. Three days later, the vein graft segments were resected. Expression of the lacZ gene was confirmed by X-Gal chromagen staining and visualization by light and transmission electron microscopy. Gene expression was apparent in all layers of the vein graft wall, with prominent staining in the adventitia. sVCAM expression was confirmed by immunohistochemistry and in situ hybridization. We conclude that ex vivo gene transfer before vein grafting is feasible using a replication-deficient recombinant adenovirus and results in a high level of gene expression in vivo. 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M</creatorcontrib><title>Adenovirus-mediated gene transfer of soluble vascular cell adhesion molecule to porcine interposition vein grafts</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The efficacy of aorto-coronary vein grafting is limited by early graft thrombosis and accelerated graft atherosclerosis. Direct adenovirus-mediated transfer of genes encoding inhibitory proteins may prevent or slow progression of vein graft disease. Recombinant adenoviruses containing the cDNA for the marker gene lacZ (Ad.CMVlacZ) or soluble vascular cell adhesion molecule (sVCAM) (Ad.CB-sVCAM) were used to infect segments of porcine jugular vein or human saphenous vein. Ex vivo testing showed expression of the introduced genes after incubation with Ad.CMVlacZ or Ad.CBsVCAM for periods from 1 to 24 hours, with an increase in transfection efficiency with increasing incubation time. Porcine jugular veins were then interposed as vascular grafts in the carotid arteries of four juvenile farm pigs after ex vivo gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or Ad.CBsVCAM. sVCAM-transfected carotid vein grafts were placed on one side and lacZ transfected veins were placed contralaterally as controls. Three days later, the vein graft segments were resected. Expression of the lacZ gene was confirmed by X-Gal chromagen staining and visualization by light and transmission electron microscopy. Gene expression was apparent in all layers of the vein graft wall, with prominent staining in the adventitia. sVCAM expression was confirmed by immunohistochemistry and in situ hybridization. We conclude that ex vivo gene transfer before vein grafting is feasible using a replication-deficient recombinant adenovirus and results in a high level of gene expression in vivo. 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Vascular system</subject><subject>Carotid Arteries - surgery</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene Expression</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Vectors</subject><subject>Graft Occlusion, Vascular - prevention &amp; control</subject><subject>Humans</subject><subject>In Situ Hybridization</subject><subject>Jugular Veins - transplantation</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Saphenous Vein - transplantation</subject><subject>Swine</subject><subject>Transfection</subject><subject>Vascular Cell Adhesion Molecule-1</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtLJDEUhYM4OO1j72YgiLirmtw8KlVLaZwZQRiQcR1SqRuNVFfapKrBf28aGxezyet-53JzDiGXwGqABn4yqNf3j3Xb1aqGjvMjsgLFZSWV6I7JijHWVVpw_p2c5vxaro3Q6oScaAUSWLsib7cDTnEX0pKrDQ7BzjjQZ5yQzslO2WOi0dMcx6Ufke5sdstoE3U4jtQOL5hDnOgmjljeiybSbUwuFHmYZkzbmMO8J3YYJvqcrJ_zOfnm7Zjx4rCfkadfd__Wf6qHv7_v17cPlZNCzFVf_ifAw9ArprhQfa-4tq2XrEHppUUFXupGaaVa58qhA-GgLL7xnfJCnJGbz77bFN8WzLPZhLyf204Yl2x0IzXjQhfw6j_wNS5pKrMZDlyDAqYKxD4hl2LOCb3ZprCx6d0AM_soDANTojBtZ5TZR1EkPw59l75Y-yU4eF_q14d6cdWOvvjtQv7CJGgGkosPwQmRjA</recordid><startdate>19940501</startdate><enddate>19940501</enddate><creator>SHI-JEN CHEN</creator><creator>WILSON, J. 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Vascular system</topic><topic>Carotid Arteries - surgery</topic><topic>Cell Adhesion Molecules - genetics</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene Expression</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Vectors</topic><topic>Graft Occlusion, Vascular - prevention &amp; control</topic><topic>Humans</topic><topic>In Situ Hybridization</topic><topic>Jugular Veins - transplantation</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Saphenous Vein - transplantation</topic><topic>Swine</topic><topic>Transfection</topic><topic>Vascular Cell Adhesion Molecule-1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SHI-JEN CHEN</creatorcontrib><creatorcontrib>WILSON, J. M</creatorcontrib><creatorcontrib>MULLER, D. W. 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Ex vivo testing showed expression of the introduced genes after incubation with Ad.CMVlacZ or Ad.CBsVCAM for periods from 1 to 24 hours, with an increase in transfection efficiency with increasing incubation time. Porcine jugular veins were then interposed as vascular grafts in the carotid arteries of four juvenile farm pigs after ex vivo gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or Ad.CBsVCAM. sVCAM-transfected carotid vein grafts were placed on one side and lacZ transfected veins were placed contralaterally as controls. Three days later, the vein graft segments were resected. Expression of the lacZ gene was confirmed by X-Gal chromagen staining and visualization by light and transmission electron microscopy. Gene expression was apparent in all layers of the vein graft wall, with prominent staining in the adventitia. sVCAM expression was confirmed by immunohistochemistry and in situ hybridization. We conclude that ex vivo gene transfer before vein grafting is feasible using a replication-deficient recombinant adenovirus and results in a high level of gene expression in vivo. The potential for this approach to prevent early vein graft thrombosis or accelerated vein graft atherosclerosis requires further evaluation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>7514108</pmid><doi>10.1161/01.CIR.89.5.1922</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; American Heart Association; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals
subjects Adenoviridae - genetics
Animals
Atherosclerosis (general aspects, experimental research)
Base Sequence
Biological and medical sciences
Blood and lymphatic vessels
Blood Vessel Prosthesis
Cardiology. Vascular system
Carotid Arteries - surgery
Cell Adhesion Molecules - genetics
Endothelium, Vascular - metabolism
Fluorescent Antibody Technique
Gene Expression
Gene Transfer Techniques
Genetic Vectors
Graft Occlusion, Vascular - prevention & control
Humans
In Situ Hybridization
Jugular Veins - transplantation
Medical sciences
Molecular Sequence Data
Saphenous Vein - transplantation
Swine
Transfection
Vascular Cell Adhesion Molecule-1
title Adenovirus-mediated gene transfer of soluble vascular cell adhesion molecule to porcine interposition vein grafts
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