Therapeutic angiogenesis following intramuscular gene transfer of vascular endothelial growth factor 121 in a dog model of hindlimb ischemia

Electronic Journal of Biotechnology (Impact Factor: 0.65). 12/2003; DOI: 10.2225/vol6-issue3-fulltext-2
Source: OAI

ABSTRACT Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, has been shown to promote therapeutic angiogenesis in animal models of critical limb ischemia. Ischemic skeletal muscle is advantageous for taking up and expressing foreign genes transferred as naked plasmid DNA. Accordingly, we investigated the hypothesis that intramuscular administration of naked plasmid DNA encoding the 121-amino acid isoform of VEGF could augment collateral development and tissue perfusion in a dog hindlimb ischemia model. Unilateral hindlimb ischemia was surgically induced in Beagle dogs. Ten days later, animals received intramuscular injections of pVEGF121 plasmid directly in the ischemic muscles. Angiogenic effects were evaluated by angiography, calf blood pressure ratio and vasomotor reserve analyses. Thirty days after gene transfer, angiographically recognizable collateral vessels were increased in pVEGF121-treated animals compared with controls. Improvement in perfusion to the ischemic limb was documented by a significantly higher calf blood pressure ratio for pVEGF121 (0.79 ± 0.05) versus controls (0.56 ± 0.14, P<0.01). Vasomotor reserve assay suggested amelioration in blood availability at the microcirculation level in pVEGF121-treated animals. Hematological variables showed no significant modification due to the treatment. Our results suggest that intramuscular gene transfer of VEGF121 may promote therapeutic angiogenesis in critical limb vascular insufficiency.

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    ABSTRACT: The field of DNA vaccine technology has experienced an increasing development during the last 10 years, being an attractive, cost effective and simple choice for researchers. Here, we focus on the relevant principles for designing an efficient pharmaceutical-grade plasmid DNA manufacturing process for human use. Plasmid DNA constructs pIDKE2S (coding for the E2 protein of the hepatitis C virus), pVEGF121 (coding for the human vascular endothelial growth factor 121) and the pCGV (coding for Gumboro's disease virus antigens as DNA immunogen in poultry) were analysed as study cases.

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Jun 4, 2014