Abstract
Restenosis from neointimal proliferation is a frequent complication of intracoronary stenting and catheter-based revascularization procedures. Currently, there is no known therapeutic strategy that has been sufficiently effective to warrant its widespread use. In the present study, the anti-proliferative properties of a matrix (collagen)-targeted retroviral vector bearing a mutant cyclin G1 (DNT 41-249) construct was evaluated in vitro and in vivo. In controlled one-month efficacy studies, the intraluminal instillation of the mutant cyclin G1 vector significantly inhibited neointima lesion formation in balloon-injured rat arteries without neointimal growth, associated necrosis or intense inflammatory reaction. Taken together, these data extend the potential utility of the matrix-targeted mutant cyclin G1 retroviral vector for management of vascular restenosis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Angioplasty, Balloon / adverse effects
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Animals
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Carotid Arteries / chemistry
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Carotid Arteries / pathology
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Carotid Artery Injuries / etiology
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Carotid Artery Injuries / genetics
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Carotid Artery Injuries / prevention & control*
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Cell Division / drug effects
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Cell Division / genetics
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Cell Line
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Cyclin G
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Cyclin G1
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Cyclins / administration & dosage*
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Cyclins / analysis
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Cyclins / genetics
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Cyclins / therapeutic use
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DNA, Antisense / genetics
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DNA, Recombinant / genetics
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Gene Transfer Techniques
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Genetic Therapy / methods
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Genetic Vectors / administration & dosage
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Humans
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Immunohistochemistry
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Mice
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Molecular Sequence Data
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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Mutation
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Rats
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Retroviridae / genetics
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Sequence Homology, Amino Acid
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Time Factors
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Treatment Outcome
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Tunica Intima / drug effects
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Tunica Intima / metabolism
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Tunica Intima / pathology*
Substances
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CCNG1 protein, human
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Ccng1 protein, mouse
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Ccng1 protein, rat
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Cyclin G
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Cyclin G1
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Cyclins
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DNA, Antisense
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DNA, Recombinant