Abstract | OBJECTIVE: METHODS: Jugular vein to carotid artery interposition vein grafts in hypercholesterolemic rabbits were treated, using pressure-mediated delivery, with either E2F decoy oligonucleotide, scrambled oligonucleotide, or vehicle alone. E2F decoy inhibition of cell-cycle gene expression was determined by measuring proliferating cell nuclear antigen upregulation and bromodeoxyuridine incorporation in vascular smooth muscle cells. Neointimal hyperplasia and atherosclerosis were compared between groups at 6 months after operation. Wall stress was derived from the ratio of luminal radius to wall thickness. Normal rabbits exposed to 6 weeks of diet-induced hypercholesterolemia starting 6 months after operation were analyzed in the same manner. RESULTS: CONCLUSION: A single intraoperative pressure-mediated delivery of E2F decoy effectively provides vein grafts with long-term resistance to neointimal hyperplasia and atherosclerosis. These findings suggest that long-term reduction in human vein graft failure rates may be feasible with this ex vivo gene therapy approach.
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Authors | A Ehsan, M J Mann, G Dell'Acqua, V J Dzau |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 121
Issue 4
Pg. 714-22
(Apr 2001)
ISSN: 0022-5223 [Print] United States |
PMID | 11279413
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antimetabolites
- Carrier Proteins
- Cell Cycle Proteins
- Cholesterol, Dietary
- DNA Probes
- DNA-Binding Proteins
- E2F Transcription Factors
- Proliferating Cell Nuclear Antigen
- Retinoblastoma-Binding Protein 1
- Transcription Factor DP1
- Transcription Factors
- Bromodeoxyuridine
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Topics |
- Anastomosis, Surgical
- Animals
- Antimetabolites
(pharmacokinetics, therapeutic use)
- Arteriosclerosis
(chemically induced, genetics, metabolism, therapy)
- Bromodeoxyuridine
(pharmacokinetics, therapeutic use)
- Carotid Artery Diseases
(chemically induced, metabolism, pathology, prevention & control)
- Carotid Artery, Common
(surgery)
- Carrier Proteins
- Cell Cycle Proteins
(genetics, therapeutic use)
- Cell Division
(drug effects)
- Cholesterol, Dietary
(toxicity)
- DNA Probes
(chemistry)
- DNA-Binding Proteins
- Disease Progression
- E2F Transcription Factors
- Genetic Therapy
(methods)
- Hypertrophy
- Jugular Veins
(metabolism, pathology, transplantation)
- Muscle, Smooth, Vascular
(drug effects, pathology)
- Proliferating Cell Nuclear Antigen
(drug effects, metabolism)
- Rabbits
- Retinoblastoma-Binding Protein 1
- Transcription Factor DP1
- Transcription Factors
(genetics, therapeutic use)
- Transfection
- Tunica Intima
(drug effects, pathology)
- Up-Regulation
(drug effects)
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