| p27-p16 fusion gene inhibits angioplasty-induced neointimal hyperplasia and coronary artery occlusion. | |
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MedLine Citation:
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PMID: 11509448 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inhibition of proliferative neointima formed by vascular smooth muscle cells is a potential target in preventing angioplasty-induced restenosis. We have created a potent antiproliferative by fusing the active regions of the p27 and p16 cell cycle inhibitors. Intravascular delivery of a replication-deficient adenoviral vector (AV) encoding this p27-p16 fusion protein, named W9, inhibited balloon injury-induced neointimal hyperplasia in rabbit carotid arteries. In a therapeutically more relevant model, AV-W9 was delivered to balloon-injured porcine coronary arteries in vivo using an infusion catheter. Of the three coronary arteries, two were injured with a 15-mm balloon catheter and either were left untreated or were treated with 10(12) viral particles of either AV-W9 or a control null virus. AV-W9 treatment significantly inhibited neointimal hyperplasia in this porcine arterial balloon injury model compared with untreated or control virus-treated vessels. The average intimal area of the AV-W9-treated group 10 days after balloon injury and treatment was 0.42+/-0.36 mm(2), whereas the AV-null group demonstrated an intimal area of 0.70+/-0.52 mm(2). At day 10 the average intimal thickness of the AV-W9-treated vessels was 9.1 microm (n=5, x 20 magnification) compared with 21.2 microm (n=5, x 20 magnification) in control virus-treated vessels. This trend was also observed at 28 days after balloon injury and gene transfer during which AV-W9-treated vessels demonstrated an average intimal thickness of 4.7 microm (n=8, x 20 magnification) compared with 13.3 microm (n=3, x 20 magnification) in control virus-treated vessels and 7.3 microm (n=5, x 20 magnification) in the sham-treated vessels. The AV-W9 treatment was safe and well tolerated. These data suggest that AV-W9 gene therapy may be useful in preventing angioplasty-induced intimal hyperplasia in the coronary artery. |
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Authors:
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L V Tsui; A Camrud; J Mondesire; P Carlson; N Zayek; L Camrud; B Donahue; S Bauer; A Lin; D Frey; M Rivkin; A Subramanian; R Falotico; J Gyuris; R Schwartz; J G McArthur |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation research Volume: 89 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-08-17 Completed Date: 2001-08-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 323-8 Citation Subset: IM |
Affiliation:
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Cell Genesys Inc., Foster City, CA 94404, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Angioplasty, Transluminal, Percutaneous Coronary / adverse effects* Animals Cell Cycle Proteins / genetics* Cells, Cultured Coronary Disease / etiology, pathology, prevention & control* Cyclin-Dependent Kinase Inhibitor p16 / genetics* Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases / antagonists & inhibitors Disease Models, Animal Female Gene Therapy / methods* Genetic Vectors / administration & dosage, genetics Heart Catheterization Humans Hyperplasia / prevention & control* Infusions, Intra-Arterial Male Muscle, Smooth, Vascular / cytology, drug effects, metabolism Rabbits Recombinant Fusion Proteins / administration & dosage, biosynthesis, genetics Swine Transduction, Genetic / methods Treatment Outcome Tumor Suppressor Proteins* Tunica Intima / pathology |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Recombinant Fusion Proteins; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.22/Cyclin-Dependent Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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