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

942 Citations (Scopus)

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

Fingerprint

Vascular Endothelial Growth Factor A
Extremities
Rabbits
Arteries
Therapeutics
Angiography
Ischemia
Physiologic Neovascularization
Pathologic Neovascularization
Arterial Occlusive Diseases
Iliac Artery
Therapeutic Uses
Femoral Artery
Mitogens
Heparin
Histology
Protein Isoforms
Endothelial Cells
Hemodynamics
Blood Pressure

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Therapeutic angiogenesis : A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. / Takeshita, Satoshi; Zheng, Lu P.; Brogi, Edi; Kearney, Marianne; Pu, Lee Li-Qun; Bunting, Stuart; Ferrara, Napoleone; Symes, James F.; Isner, Jeffrey M.

In: Journal of Clinical Investigation, Vol. 93, No. 2, 02.1994, p. 662-670.

Research output: Contribution to journalArticle

Takeshita, S, Zheng, LP, Brogi, E, Kearney, M, Pu, LL-Q, Bunting, S, Ferrara, N, Symes, JF & Isner, JM 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, vol. 93, no. 2, pp. 662-670.
Takeshita, Satoshi ; Zheng, Lu P. ; Brogi, Edi ; Kearney, Marianne ; Pu, Lee Li-Qun ; Bunting, Stuart ; Ferrara, Napoleone ; Symes, James F. ; Isner, Jeffrey M. / Therapeutic angiogenesis : A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. In: Journal of Clinical Investigation. 1994 ; Vol. 93, No. 2. pp. 662-670.
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