Therapeutic angiogenesis induced by human hepatocyte growth factor gene in hindlimb ischemia of dogs

A preclinical study of treating peripheral ar-tery occlusive disease (PAD) was performed by using ahepatocyte growth factor (HGF) gene-expressing vector,plasmid pUDKH, in a dog model with complete ischemia of one hindlimb. After ligation of femoral artery of onehindlimb, pUDKH was transferred directly into the ischemic limb muscles. The angiogenic activity of the plasmid pUDKH was evaluated. On D 30 after injecting once of pUDKH at different doses into local muscles immediately after opera-tion, the degree of augmentation of collateral vessel forma-tion was significantly greater than that treated by blankvector. In addition, the blood flow rate of femoral artery in dogs treated with pUDKH was recovered on D 90, while the flow rate was only 1/5 to 1/3 in control dogs. The pulse am-plitude of pUDKH-treated dogs was recovered on D 90, but it was hardly detectable in most of the control dogs. The sideeffects of intramuscular transfection of pUDKH were alsoinvestigated, and no significant positive change was found. It is suggested that angiogenesis induced by HGF gene has the potential for clinical use in the treatment of peripheral arte-rial diseases.