| Gene therapy in cardiac surgery: intramyocardial injection of naked plasmid DNA for chronic myocardial ischemia. | |
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MedLine Citation:
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PMID: 14583313 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Growth factor gene therapy represents one current approach in the therapy of myocardial ischemia. We assessed the in vitro and in vivo expression of naked plasmid DNA aiming at preservation of function in a chronically ischemic myocardial model. METHODS: In vitro: Primary cardiac fibroblasts were transfected with plasmids encoding enhanced green fluorescent protein, human VEGF(121), human FGF-2, or porcine MCP-1. Protein synthesis was assessed microscopically, by ELISA, Western blotting, or intracellular immunofluorescence. In vivo: A LAD stenosis was created in healthy pigs. One week later, segmental myocardial shortening (SMS) and systemic hemodynamics (left ventricular stroke work index, LVSWI, time derivative of left ventricular pressure, dp/dt(max)) were assessed at baseline. Afterwards, the ischemic area received either intramyocardial injections of naked cytokine plasmid DNA or vector only, or was left untreated. One myocardial sample taken 1 h after plasmid injection was subjected to RT-PCR and PCR. After 3 months, cardiac function was re-examined. RESULTS: In vitro: Transfection of cardiac fibroblasts resulted in high gene expression for several days. In vivo: Plasmid-specific DNA and mRNA were found 1 h after plasmid injection (n=1). After 3 months, VEGF, FGF-2, and vector rendered better results of regional contractility at rest and of LVSWI. However, only VEGF and FGF-2 were effective with regard to regional contractility under dobutamine stress and to left ventricular contractility. CONCLUSION: In conclusion, intramyocardial injection of naked plasmid DNA encoding VEGF(121) or FGF-2 improved myocardial function in chronic ischemia in more aspects than vector only and was superior to untreated ischemia or MCP-1. This strategy can be considered a successful tool for growth factor stimulated preservation of function in chronic myocardial ischemia. |
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Authors:
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Claudia A U Heilmann; Tim Attmann; Alexander Thiem; Eric Haffner; Friedhelm Beyersdorf; Georg Lutter |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Volume: 24 ISSN: 1010-7940 ISO Abbreviation: Eur J Cardiothorac Surg Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-10-29 Completed Date: 2004-03-25 Revised Date: 2007-05-02 |
Medline Journal Info:
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Nlm Unique ID: 8804069 Medline TA: Eur J Cardiothorac Surg Country: England |
Other Details:
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Languages: eng Pagination: 785-93 Citation Subset: IM |
Affiliation:
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Department of Cardiovascular Surgery, University Hospital Freiburg, Freiburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Chemokine CCL2 / genetics, metabolism Chronic Disease Fibroblast Growth Factor 2 / genetics, metabolism Fibroblasts / metabolism Gene Expression Gene Therapy / methods* Growth Substances / genetics*, metabolism Humans Myocardial Contraction Myocardial Ischemia / metabolism, physiopathology, therapy* Plasmids / genetics Swine Transfection / methods Vascular Endothelial Growth Factor A / genetics, metabolism Ventricular Function, Left |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL2; 0/Growth Substances; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 103107-01-3/Fibroblast Growth Factor 2 |
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