Document Detail


Gene therapy in cardiac surgery: intramyocardial injection of naked plasmid DNA for chronic myocardial ischemia.
MedLine Citation:
PMID:  14583313     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Claudia A U Heilmann; Tim Attmann; Alexander Thiem; Eric Haffner; Friedhelm Beyersdorf; Georg Lutter
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Publication Detail:
Type:  Journal Article    
Journal Detail:
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:
Created Date:  2003-10-29     Completed Date:  2004-03-25     Revised Date:  2007-05-02    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  England    
Other Details:
Languages:  eng     Pagination:  785-93     Citation Subset:  IM    
Affiliation:
Department of Cardiovascular Surgery, University Hospital Freiburg, Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
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:
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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