Abstract
Combinatorial strategy has been used in therapeutic angiogenesis in animal models of peripheral arterial disease (PAD) and coronary artery disease for decades. Previous studies have shown that basic fibroblast growth factor (FGF-2) and platelet-derived growth factor BB (PDGF-BB) proteins together establish functional and stable vascular networks on mouse corneal and also in animal model of hindlimb ischemia. However, the short half life of protein by single injection is not sufficient to achieve effective dosage, repeated and prolonged injection causes systemic toxicity. Here we study the synergistic effects of FGF-2 and PDGF-BB by intramuscular injection of naked plasmid DNA on therapeutic angiogenesis in rabbit model of hindlimb ischemia. We found that transient delivery of FGF-2 and PDGF-BB naked DNA together resulted in greater increases in capillary growth, collateral formation and popliteal blood flow compared with control and single gene delivery. Our data provided novel evidence of beneficial effects of DNA-based FGF-2 and PDFG-BB on muscle repair after ischemic injury. These findings reveal an alternative therapeutic approach in the treatment of ischemic diseases and even in muscular disorders.
Copyright 2010. Published by Elsevier Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Angiogenesis Inducing Agents / pharmacology
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Angiogenesis Inducing Agents / therapeutic use
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Angiography
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Animals
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Becaplermin
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Femoral Artery / surgery
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / pharmacology
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Fibroblast Growth Factor 2 / therapeutic use*
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Genetic Therapy / methods
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Genetic Vectors / administration & dosage
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Hindlimb / blood supply
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Hindlimb / drug effects*
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Hindlimb / pathology
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Hindlimb / physiology
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Humans
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Iliac Artery / drug effects
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Iliac Artery / physiology
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Ischemia / pathology
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Ischemia / therapy*
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Microvessels / drug effects
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Microvessels / growth & development
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Microvessels / metabolism
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Muscle, Skeletal / blood supply
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiology*
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Neovascularization, Physiologic / drug effects*
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
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Platelet-Derived Growth Factor / genetics
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Platelet-Derived Growth Factor / pharmacology
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Platelet-Derived Growth Factor / therapeutic use*
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Popliteal Artery / drug effects
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Popliteal Artery / physiology
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Proto-Oncogene Proteins c-sis
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Rabbits
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Regeneration / drug effects*
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Regional Blood Flow / drug effects
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Regional Blood Flow / physiology
Substances
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Actins
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Angiogenesis Inducing Agents
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Platelet Endothelial Cell Adhesion Molecule-1
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Platelet-Derived Growth Factor
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Proto-Oncogene Proteins c-sis
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Fibroblast Growth Factor 2
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Becaplermin