Therapeutic angiogenesis: A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model

Satoshi Takeshita, Lu P. Zheng, Edi Brogi, Marianne Kearney, Lee Li-Qun Pu, Stuart Bunting, Napoleone Ferrara, James F. Symes, Jeffrey M. Isner

Research output: Contribution to journalArticle

948 Scopus citations

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 intrarterial 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 μg 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.

Original languageEnglish (US)
Pages (from-to)662-670
Number of pages9
JournalJournal of Clinical Investigation
Volume93
Issue number2
StatePublished - Feb 1994
Externally publishedYes

Keywords

  • Angiography
  • Capillaries
  • Collateral arteries
  • Endothelial cell
  • Peripheral arteries

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Therapeutic angiogenesis: A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model'. Together they form a unique fingerprint.

  • Cite this

    Takeshita, S., Zheng, L. P., Brogi, E., Kearney, M., Pu, L. L-Q., Bunting, S., Ferrara, N., Symes, J. F., & Isner, J. M. (1994). Therapeutic angiogenesis: A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. Journal of Clinical Investigation, 93(2), 662-670.