| Autologous vascular smooth muscle cell-based myocardial gene therapy to induce coronary collateral growth. | |
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MedLine Citation:
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PMID: 15277192 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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For therapeutic angiogenesis to achieve clinical relevance, it must be effective, with minimal side effects to other end organ systems. We developed a cardiac-specific gene delivery mechanism by transfecting autologous vascular smooth muscle cells (VSMC) with VEGF and administering these cells via intracoronary injection. We evaluated the efficacy of this protocol by its ability to stimulate angiogenesis in the presence of a subthreshold stimulus for collateralization. A modified canine repetitive coronary occlusion model was utilized in these experiments with left anterior descending coronary artery occlusions for 2 min every 2 h four times per day for 21 days. An intramyocardial catheter in the perfusion territory of the left anterior descending coronary artery measured proteins in the myocardial interstitial fluid. VSMC from jugular vein explants were isolated, amplified in culture for 3 wk, and transfected with a plasmid expressing VEGF-165 and/or enhanced green fluorescent protein. Cells were injected before commencement of occlusions. VEGF levels in myocardial interstitial fluid were significantly higher in VEGF-transfected animals than in sham (repetitive occlusions without cell transplantation) and control (repetitive occlusions with enhanced green fluorescent protein-transfected cells) animals at the onset of occlusions (P < 0.05). In the VEGF group, collateral flow was increased at day 7 and remained higher than in sham and control groups thereafter. We found that intracoronary administration of VEGF-transfected autologous VSMC effectively promotes collateral development. This approach may provide a way to confine delivery of a gene to a specified organ, thus minimizing complications related to gene transfection in nontargeted organ systems. |
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Authors:
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Naoichiro Hattan; David Warltier; Weidong Gu; Christopher Kolz; William M Chilian; Dorothee Weihrauch |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 287 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-27 Completed Date: 2004-09-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H488-93 Citation Subset: IM |
Affiliation:
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Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. nhatta@lsuhsc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkaline Phosphatase
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metabolism Animals Cardiac Surgical Procedures* Coronary Circulation* Dogs Female Gene Therapy / methods* Green Fluorescent Proteins Indicators and Reagents / metabolism Luminescent Proteins / genetics, metabolism Male Muscle, Smooth, Vascular / cytology*, metabolism Myocardium / metabolism Myocytes, Smooth Muscle / metabolism, transplantation* Neovascularization, Physiologic* Transfection Vascular Endothelial Growth Factor A / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-32788/HL/NHLBI NIH HHS; HL-54280/HL/NHLBI NIH HHS; HL-65203/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Indicators and Reagents; 0/Luminescent Proteins; 0/Vascular Endothelial Growth Factor A; 147336-22-9/Green Fluorescent Proteins; EC 3.1.3.1/Alkaline Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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