Therapeutic Angiogenesis

Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested thatVEGF is a regulator ofnaturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165amino acid isoform ofVEGF was administered as a single intraarterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,090,g of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.75±0.14 vs. 0.48±0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease. (J. Clin. Invest. 1994. 93:662670.)