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(Circulation. 1996;94:3062-3064.)
© 1996 American Heart Association, Inc.
Articles |
A Little VEGF Goes a Long Way
Therapeutic Angiogenesis by Direct Injection of Vascular Endothelial Growth Factor–Encoding Plasmid DNA
the Departments of Pathology and Cell Biology, Baylor College of Medicine, Houston, Tex.
Correspondence to Dr Mark Majesky, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail mmajesky@bcm.tmc.edu.
Key Words: Editorials • angiogenesis • ischemia • genes • peripheral vascular disease
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Introduction |
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Local production of small amounts of a potent, secreted growth factor with built-in specificity for endothelial cells may bypass the need for highly efficient gene transfer vectors and elaborate treatment protocols to produce effective therapeutic angiogenesis in ischemic peripheral vascular disease. That is the message of a report by Tsurumi et al that appears in this issue of Circulation1 in which naked plasmid DNA encoding the 165–amino acid secreted form of human vascular endothelial growth factor (hVEGF-165) is introduced by direct intramuscular injection into ischemic rabbit hindlimbs. Thirty days after injection of 100 µg hVEGF-165 plasmid DNA at each of five sites within ischemic hindlimb muscles, increased collateral vessel formation, improved blood flow, and an increased number of capillary profiles could be demonstrated compared with control hindlimbs that received injections of plasmid DNA only. The simplicity of the gene transfer approach described in this study suggests a potentially useful alternative for patients with extensive peripheral vascular disease in whom intravascular angioplasty catheter–based gene delivery methods are inadvisable or not possible.
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VEGF: An Endothelial Cell–Specific Ligand and Receptor Signaling Pair |
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VEGF was discovered in the early 1980s by Dvorak and coworkers as a factor that made blood vessels leaky; hence, it was given the name of vascular permeability factor (VPF).2 3 Then, in the late 1980s, several groups showed that VEGF/VPF stimulated endothelial cell migration and replication and was a potent angiogenic factor in vivo.4 5 6 VEGF is a heat-stable, 46-kD dimeric protein with structural similarity to placenta growth factor (PlGF) (
53% amino acid identity) and more distant homology (18% to This article has been cited by other articles:
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  A. W. Ashton and J. A. Ware Thromboxane A2 Receptor Signaling Inhibits Vascular Endothelial Growth Factor-Induced Endothelial Cell Differentiation and Migration Circ. Res., August 20, 2004; 95(4): 372 - 379. [Abstract] [Full Text] [PDF]
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 H. Su, J. Arakawa-Hoyt, and Y. W. Kan Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model PNAS, July 9, 2002; 99(14): 9480 - 9485. [Abstract] [Full Text] [PDF]
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 E. R. Schwarz, M. T. Speakman, M. Patterson, S. S. Hale, J. M. Isner, L. H. Kedes, and R. A. Kloner Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat--angiogenesis and angioma formation J. Am. Coll. Cardiol., April 1, 2000; 35(5): 1323 - 1330. [Abstract] [Full Text] [PDF]
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 V. Ollivier, S. Bentolila, J. Chabbat, J. Hakim, and D. de Prost Tissue Factor-Dependent Vascular Endothelial Growth Factor Production by Human Fibroblasts in Response to Activated Factor VII Blood, April 15, 1998; 91(8): 2698 - 2703. [Abstract] [Full Text] [PDF]
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 B. S Lewis, M. Y Flugelman, A. Weisz, I. Keren-Tal, and W. Schaper Angiogenesis by gene therapy: a new horizon for myocardial revascularization? Cardiovasc Res, September 1, 1997; 35(3): 490 - 497. [Abstract] [Full Text] [PDF]
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