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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/2248

Title: RESEARCH ARTICLE - Therapeutic angiogenesis following intramuscular gene transfer of vascular endothelialgrowth factor 121 in a dog model of hindlimb ischemia
Authors: Ojalvo, Ariana G.
Seralena, Alina
Vázquez, Raysa
Montequín, José F.
Vispo, Nelson S.
Silva, Ricardo
Aldama, Alfredo
Puchades, Yaquelin
Sorell, Luis T.
Lopez-Saura, Pedro
Alfonso, María A.
Simón, Rafael
Ali, Alfonso
Seuc, Armando
Herrera, Luis
Keywords: Biotechnology
collateral development, gene therapy, naked plasmid DNA, peripheral vascular disease, revascularization. ej03025
Issue Date: Dec-2003
Publisher: Universidad Católica de Valparaíso
Citation: Electronic Journal of Biotechnology 6(3)
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.
URI: http://bioline.utsc.utoronto.ca/archive/00001379/02/ej03025.pdf
Appears in Collections:Bioline International Legacy Collection

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