Journal article
Augmented Adenovirus-Mediated Gene Transfer to Atherosclerotic Vessels
Arteriosclerosis, thrombosis, and vascular biology, Vol.17(9), pp.1786-1792
09/1997
DOI: 10.1161/01.ATV.17.9.1786
PMID: 9327778
Abstract
Vascular endothelium is an important target for gene transfer in atherosclerosis. In this study, we examined gene transfer to normal and atherosclerotic blood vessels from two species, using an organ culture method. Using normal aorta, we determined optimal dose, duration of exposure to adenovirus, and duration of incubation of vessels in tissue culture. Aortas from normal and atherosclerotic monkeys were cut into rings and incubated for 2 hours with a recombinant adenovirus, carrying the reporter gene for beta-galactosidase driven by a cytomegalovirus (CMV) promoter. After 20 hours of incubation, transgene expression was assessed with a morphometric method after histochemical staining and a chemiluminescent assay of enzyme activity. Expression of beta-galactosidase after histochemical staining, expressed as percentage of total cells, was similar in adventitial cells of normal monkeys (21 +/- 4%, mean +/- SE%) and atherosclerotic monkeys (25 +/- 12%). Transgene expression in endothelium was higher in atherosclerotic than in normal vessel (53 +/- 3% versus 27 +/- 7%, P < .05). Chemiluminescent assay indicated greater beta-galactosidase activity (2.5 +/- 0.6 mU/mg of protein) in the intima and media of atherosclerotic than normal vessels (0.6 +/- 0.2 mU/mg of protein, P < .05). Aortas from normal (n = 6) and atherosclerotic (n = 5) rabbits also were examined. Transgene expression (after histochemical staining) in endothelium was much greater in atherosclerotic than normal rabbits (39 +/- 3% versus 9 +/- 2%, P < .05) and expression in adventitial cells was similar (normal 23 +/- 2%, atherosclerotic 24 +/- 4%). Chemiluminescent assay indicated greater beta-galactosidase activity (1.2 +/- 0.4 mU/mg of protein) in the intima and media of atherosclerotic than normal vessels (0.2 +/- 0.1 mU/mg protein, P < .05). These findings suggest that an adenoviral vector with a CMV promoter provides similar transgene expression in adventitia of both normal and atherosclerotic vessels. Gene transfer to the endothelium was much more effective in atherosclerotic than in normal vessels. Thus it may be possible to achieve greater transgene expression in atherosclerotic than in normal arteries.
Details
- Title: Subtitle
- Augmented Adenovirus-Mediated Gene Transfer to Atherosclerotic Vessels
- Creators
- Hiroaki Ooboshi - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City, Iowa 52242C. David Rios - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City, Iowa 52242Yi Chu - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City, Iowa 52242Stuart D Christenson - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City, Iowa 52242Frank M Faraci - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City, Iowa 52242Beverly L Davidson - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City, Iowa 52242Donald D Heistad - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, and the Veterans Administration Medical Center, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.17(9), pp.1786-1792
- DOI
- 10.1161/01.ATV.17.9.1786
- PMID
- 9327778
- NLM abbreviation
- Arterioscler Thromb Vasc Biol
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 09/1997
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040498802771
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