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Dose‐Dependent Neovascularization‐Promoting Effect of Adenovirus Vector CI‐1023 in a Rat Hindlimb Ischaemic Model
Author(s) -
Wang He,
Keiser Joan A.,
Olszewski Bronia,
Brammer David,
Gordon David
Publication year - 2004
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2004.950206.x
Subject(s) - neovascularization , hindlimb , vascular endothelial growth factor , perfusion , growth factor , angiogenesis , medicine , chemistry , endocrinology , vegf receptors , receptor
Abstract: CI‐1023 (Ad GV VEGF121.10) is a replication‐deficient adenovirus vector (complete E1a − , partial E1b − , partial E3 − ) delivering human vascular endothelial growth factor‐121 gene. Previous studies from this group have established that CI‐1023 can successfully transfer human vascular endothelial growth factor‐121 gene resulting in local tissue expression of vascular endothelial growth factor protein. The purpose of this study was to evaluate neovascularization‐promoting potency and efficacy of CI‐1023 in a wide dose range. In a rat hindlimb ischaemic model, we measured neovascularization‐promoting effect of CI‐1023 using three end‐points: post mortem angiography, immuno‐histochemisty and Laser Doppler scanning of tissue blood perfusion. Neovascularization‐promoting activity of CI‐1023 over the dose range of 4×10 6 pu−4×10 10 pu was evaluated. Our data demonstrated an obvious dose‐dependent effect between 4×10 6 pu−4×10 8 pu. The neovascularizing effect is somewhat plateaued at the levels between 4×10 8 pu and 4×10 10 pu. We conclude CI‐1023 is a potent neovascularization‐promoting compound, with a dose‐dependent effect between 4×10 6 pu−4×10 8 pu in the rat hindlimb ischaemic model.