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| THERAPEUTIC ANGIOGENESIS - A SINGLE INTRAARTERIAL BOLUS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AUGMENTS REVASCULARIZATION IN A RABBIT ISCHEMIC HIND-LIMB MODEL |
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| Author(s): TAKESHITA S, ZHENG LP, BROGI E, KEARNEY M, PU LQ, BUNTING S, FERRARA N, SYMES JF, ISNER JM |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 93 Issue: 2 Pages: 662-670 Published: FEB 1994 |
| Times Cited: 667 References: 45 |
| Abstract: Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally 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 165-amino acid isoform of VEGF 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 500-1,000 mu 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, 0.7 +/- 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. TUFTS UNIV, SCH MED, ST ELIZABETHS MED CTR, DEPT MED CARDIOL, BOSTON, MA 02135 USA
2. TUFTS UNIV, SCH MED, ST ELIZABETHS MED CTR, DEPT SURG CARDIOVASC, BOSTON, MA 02135 USA
3. TUFTS UNIV, SCH MED, ST ELIZABETHS MED CTR, DEPT BIOMED RES, BOSTON, MA 02135 USA
4. MCGILL UNIV, ROYAL VICTORIA HOSP, DEPT SURG, MONTREAL H3A 1A1, PQ CANADA
5. GENENTECH INC, DEPT CARDIOVASC RES, S SAN FRANCISCO, CA 94080 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: MY296 |
| ISSN: 0021-9738 |
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