Angiogenesis. Angiogenic therapy using fibroblast growth factors and vascular endothelial growth factors for ischemic vascular lesions.

Angiogenic therapy using fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) is being developed as a novel therapeutic strategy to obtain restoration of blood flow around the ischemia in cases of ischemic cardiovascular disease. In addition, arterial gene therapy through gene transfer by VEGF genes has now reached the stage of clinical application. Through in vivo animal experiments to determine the angiogenic effects of FGF and VEGF, we hope to obtain clues concerning the clinical applications of these methods. Methods-1: Twenty-three adult dogs were divided into 3 groups as follows: Group A-1: 20 micrograms of bFGF was administered intravenously simultaneously with heparin three times per week in 4 dogs. Group A-2: 20 micrograms of bFGF was administered intravenously three times a week without heparin in 4 dogs. Group B: 20 micrograms of bFGF was administered intramuscularly three times per week in 5 dogs. Group C: Sham operation control group consisting of 10 dogs. Local ischemia was created in the hind limbs of animals in groups A-1, A-2 and B through ligation of the femoral artery. Selective femoral arteriography was performed immediately after ligation at 1 week and 2 weeks postoperatively. Biopsy was also performed either at 1 week or 2 weeks after ligation. Results-1: (1) The percent increase in number of collateral vessels of the ischemic zone, as recognized on arteriography, was greater in the bFGF groups compared to group C. (2) The increase in collateral vessels peaked at 1 week. (3) No difference in angiogenic effect was observed in relation to the method of administration. (4) The combined administration of heparin had no angiogenic effect. (5) The hemoglobin content of the biopsy specimens was significantly greater in the 3 groups receiving bFGF compared to group C. Methods-2: The same study was performed using VEGF as detailed in Method-1. Results-2: As in the first experiment, a significant increase in collateral vessels was seen in the VEGF group compared to the control group. Both exogenous bFGF and VEGF significantly promote collateral vessel development and appear to be effective novel therapeutic agents for the treatment of ischemic disease.