Enhanced Therapeutic Angiogenesis by Cotransfection of Prostacyclin Synthase Gene or Optimization of Intramuscular Injection of Naked Plasmid DNA

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)

Acceleration of wound healing by combined gene transfer of hepatocyte growth factor and prostacyclin synthase with Shima Jet

“…Quantitative analysis also showed no tendency for an increase in blood flow (Figure 5b). This result does not seem to be consistent with our previous report; 26,27 however, this assay was performed on day 4 and it seemed too short to induce angiogenesis, indicating that our results of this study are reasonable. On the other hand, additional PGIS gene transfer to HGF gene transfer increased the blood flow even at 4 days ( Figure 5a).…”

“…26,27 Because Laser Doppler flow velocity correlates with capillary density, we measured skin blood flow by LDI. Consecutive measurements were obtained over the same regions of interest by averaging four sites around the wound.…”

“…[23][24][25] Co-transfer of HGF and PGIS genes in a murine ischemic limb model has been reported to increase the concentration of HGF protein and resulted in a significant increase in blood flow and capillary density compared with transfer of HGF gene alone. 26,27 Based on these results, we examined the effects of co-transfer of HGF and PGIS genes by the Shima Jet on wound healing in this study.…”

Altered Angiogenesis in Caveolin-1 Gene–Deficient Mice Is Restored by Ablation of Endothelial Nitric Oxide Synthase

“…Prostacyclin synthase produces the potent vasodilator prostacyclin in response to VEGF 54 and promotes angiogenesis. 55,56 Prostacyclin synthase is located in caveolae where it interacts with caveolin-1. 57 The angiopoietin receptor TEK/Tie2 exerts tight control on angiogenesis (maintaining them quiescent on angiopoetin-1 binding, but promoting endothelial cell activation on angiopoietin-2 binding) and has also been suggested to localize in endothelial cell caveolae.…”

Endothelial-Like Progenitor Cells Engineered to Produce Prostacyclin Rescue Monocrotaline-Induced Pulmonary Arterial Hypertension and Provide Right Ventricle Benefits

“…Several different gene and cell-based therapies have been proposed for treating patients with PAH, and cell therapy using endothelial progenitor cells has been shown to provide benefits in animal models. 5,11,12 Therapeutic approaches have included the use of the PGIS gene alone 13,14 or ELPCs transfected with the eNOS gene. 5 The latter approach was effective in rats with MCT-induced PAH, 5 producing results similar to those described here for our COX1-PGIS-expressing ELPCs.…”