| MicroRNAs are involved in many critical biological functions, including angiogenesis. miR-126 is an important endothelial specific angiomiR which targets negative inhibitors of the VEGF-A angiogenesis pathway. We applied ultrasound mediated gene delivery (UMGD) for miR-126 and VEGF-A delivery in a clinically relevant chronic ischemia model with Fischer and Zucker diabetic fatty (ZDF) rats. In vitro, miR-126 transfected HUVECs showed greater angiogenic potential with increased tube formation and migration response. UMGD of miR-126 produced targeted vascular transfection in rat hindlimb skeletal muscle lasting for >3 days, and resulting in inhibition of SPRED-1 and PIK3R2 protein. ZDF rats showed a significant decrease of miR-126. The dual delivery of miR-126 and VEGF-A to the ischemic leg with UMGD resulted in greatest microvascular blood improvement, vessel density, enhanced arteriolar formation than either VEGF-A or miR-126 therapy alone. UMGD is therefore a promising platform for multiple gene and miRNA delivery, with applications for therapeutic angiogenesis. |
