RGD Reference Report - Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA. - Rat Genome Database

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Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA.

Authors: Hiraoka, Kazuya  Koike, Hiromi  Yamamoto, Seiji  Tomita, Naruya  Yokoyama, Chieko  Tanabe, Tadashi  Aikou, Takashi  Ogihara, Toshio  Kaneda, Yasufumi  Morishita, Ryuichi 
Citation: Hiraoka K, etal., Circulation. 2003 Nov 25;108(21):2689-96. doi: 10.1161/01.CIR.0000093275.78676.F4. Epub 2003 Oct 20.
RGD ID: 401960079
Pubmed: PMID:14568901   (View Abstract at PubMed)
DOI: DOI:10.1161/01.CIR.0000093275.78676.F4   (Journal Full-text)


BACKGROUND: Although clinical trials of therapeutic angiogenesis by angiogenic growth factors with intramuscular injection of naked plasmid DNA have been successful, there are still unresolved problems such as low transfection efficiency. From this viewpoint, we performed the following modifications: (1) combination with vasodilation using prostacyclin and (2) changing the agents or volume of naked plasmid DNA in vivo.
METHODS AND RESULTS: First, we examined cotransfection of the VEGF gene with the prostacyclin synthase gene in a mouse hindlimb ischemia model. Cotransfection of the VEGF gene with the prostacyclin synthase gene resulted in a further increase in blood flow and capillary density compared with single VEGF gene. Similar results were obtained with other angiogenic growth factors, such as hepatocyte growth factor (HGF). Alternatively, we changed the injection volume of the solution of plasmid DNA. Luciferase activity was increased in a volume-dependent manner. An increase in injection volume at 1 site rather than separate injections at multiple sites resulted in high transfection efficiency, which suggests that transfection of naked plasmid DNA is mediated by pressure. Interestingly, treatment with hyperbaric oxygen increased the transfection efficiency. Finally, we also examined the effects of different solutions. Saline and PBS, but not water, achieved high transfection efficiency. In addition, sucrose solution but not glucose solution resulted in high luciferase activity.
CONCLUSIONS: Overall, angiogenesis might be enhanced by cotransfection of prostacyclin synthase gene or an increase in injection volume and osmotic pressure. These data provide important information for the clinical application of therapeutic angiogenesis to treat peripheral arterial disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanlimb ischemia treatmentIMP human gene in a mouse modelRGD 
PtgisRatlimb ischemia treatmentISOPTGIS (Homo sapiens)human gene in a mouse modelRGD 
PtgisMouselimb ischemia treatmentISOPTGIS (Homo sapiens)human gene in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information