Multigene Therapy by Ultrasound-mediated Plasmid Delivery: Temporally Separated Delivery of Vascular Endothelial Growth Factor and Angiopoietin-1 Promotes Sustained Angiogenesis in Chronically Ischemic Skeletal Muscle

• Main Author: Smith, Alexandra Helen
• Other Authors: Leong-Poi, Howard
• Language: en_ca
• Published: 2010
• Subjects: cardiovascular disease; angiogenesis; gene therapy; ultrasound; 0564
• Online Access: http://hdl.handle.net/1807/25804

Endogenously, VEGF initiates angiogenesis, then later Angiopoietin (Ang)-1 matures vessels. We hypothesized that multigene therapy of VEGF before Ang1 to ischemic hindlimb tissue would result in persistent angiogenesis. At 2, 4 and 8 wks after inducing ischemia, blood flow was assessed by contrast-enhanced ultrasound. Animals were treated with VEGF at 2 wks, VEGF/Ang1 at 2 wks, or VEGF at 2 wks and Ang1 at 4 wks. In untreated controls, blood flow remained reduced. After VEGF delivery, resting flow and vessel density increased; however, flow reserve remained reduced, and vasculature was capillary-rich and eventually regressed. After VEGF/Ang1 co-delivery, flow increased marginally, flow reserve improved and vascular architecture remained normal. After separated VEGF and Ang1 delivery, flow, vessel density and flow reserve increased and were sustained, while vascular architecture remained normal. In conclusion, temporally separated VEGF and Ang1 delivery promotes sustained angiogenesis and improved vessel functionality.