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Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA.
Circulation. 2003 Nov 25; 108(21):2689-96.Circ

Abstract

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.

Authors+Show Affiliations

Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14568901

Citation

Hiraoka, Kazuya, et al. "Enhanced Therapeutic Angiogenesis By Cotransfection of Prostacyclin Synthase Gene or Optimization of Intramuscular Injection of Naked Plasmid DNA." Circulation, vol. 108, no. 21, 2003, pp. 2689-96.
Hiraoka K, Koike H, Yamamoto S, et al. Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA. Circulation. 2003;108(21):2689-96.
Hiraoka, K., Koike, H., Yamamoto, S., Tomita, N., Yokoyama, C., Tanabe, T., Aikou, T., Ogihara, T., Kaneda, Y., & Morishita, R. (2003). Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA. Circulation, 108(21), 2689-96.
Hiraoka K, et al. Enhanced Therapeutic Angiogenesis By Cotransfection of Prostacyclin Synthase Gene or Optimization of Intramuscular Injection of Naked Plasmid DNA. Circulation. 2003 Nov 25;108(21):2689-96. PubMed PMID: 14568901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA. AU - Hiraoka,Kazuya, AU - Koike,Hiromi, AU - Yamamoto,Seiji, AU - Tomita,Naruya, AU - Yokoyama,Chieko, AU - Tanabe,Tadashi, AU - Aikou,Takashi, AU - Ogihara,Toshio, AU - Kaneda,Yasufumi, AU - Morishita,Ryuichi, Y1 - 2003/10/20/ PY - 2003/10/22/pubmed PY - 2003/12/10/medline PY - 2003/10/22/entrez SP - 2689 EP - 96 JF - Circulation JO - Circulation VL - 108 IS - 21 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/14568901/Enhanced_therapeutic_angiogenesis_by_cotransfection_of_prostacyclin_synthase_gene_or_optimization_of_intramuscular_injection_of_naked_plasmid_DNA_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000093275.78676.F4?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -