| Focal arterial transgene expression after local gene delivery. | |
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MedLine Citation:
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PMID: 11521130 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Gene therapy for the treatment of vascular disease is limited by a low transfection efficiency and/or undesired biological responses. OBJECTIVE: To determine the transfection efficiency of delivering a liposome/DNA complex into balloon-injured rabbit arteries systematically or using a local delivery catheter. METHODS: The cationic liposomes N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl-sulphate and dioleoyl-phosphatidylethanolamine were mixed 1:1 (wt/wt) and combined with the plasmid pCMV-AP containing the human placental alkaline phosphatase (AP) reporter gene. Before initiating the in vivo experiments, the optimal ratio of liposome to DNA complex and the persistence of transgene expression were determined in cultured vascular smooth muscle cells (SMC). In vivo, a Dispatch catheter was used for local delivery of the liposome/DNA complex into rabbit iliac arteries that had been balloon injured five days previously. The contralateral iliac or renal artery was also balloon injured, and liposomes with normal saline were delivered as a negative control. For the systemic delivery group, the liposome/DNA complex was delivered through an ear vein. RESULTS: AP expression in transfected SMC persisted for 28 days in vitro, although the percentage of transfected cells declined with time (eg, at 24 h it was 27.3%+/-2.9%, at 28 days it was 0.4%+/-0.1%). SMC proliferation in vitro enhanced the transfection efficiency 12-fold. In vivo, local delivery resulted in low levels of transfection in arteries harvested one day postdelivery; however, six of seven arteries harvested three days postdelivery had multiple regions of focal transgene expression involving all three arterial layers. For the systemic delivery group, two of nine arteries expressed the transgene. No transgene expression was found in uninjured arteries in either the local or systemic delivery groups. However, with both local and systemic delivery, balloon-injured arteries that received liposomes and saline showed low levels of AP expression in either the neointima, media or adventitia, presumably due to systemic recirculation of the liposome/AP construct. CONCLUSIONS: Liposome-mediated gene transfection can be successfully performed to all vessel layers in vivo by using a local delivery catheter, and may provide a therapeutic opportunity for modulating atherosclerosis and restenosis. Unwanted transfection at a distance may occur with catheter-based local delivery and requires further refinement. |
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Authors:
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X Ma; C Glover; H Miller; J Goldstein; E O'Brien |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Canadian journal of cardiology Volume: 17 ISSN: 0828-282X ISO Abbreviation: Can J Cardiol Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-08-24 Completed Date: 2001-09-20 Revised Date: 2008-04-09 |
Medline Journal Info:
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Nlm Unique ID: 8510280 Medline TA: Can J Cardiol Country: Canada |
Other Details:
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Languages: eng Pagination: 873-83 Citation Subset: IM |
Affiliation:
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Vascular Biology Laboratory, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Cells, Cultured Disease Models, Animal Gene Expression* Gene Therapy / methods Gene Transfer Techniques* Humans Iliac Artery Muscle, Smooth, Vascular / pathology* Rabbits Sensitivity and Specificity Transgenes* Vascular Diseases / therapy |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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