Journal article
Adenovirus-mediated gene transfer to cerebral circulation
Mechanisms of ageing and development, Vol.116(2), pp.95-101
2000
DOI: 10.1016/S0047-6374(00)00123-8
PMID: 10996009
Abstract
Gene therapy may, be a promising approach for treatment of cerebrovascular disease. An adenoviral vector encoding beta-galactosidase was administered intracisternally or intraventricularly into the brain of rats. Efficient expression of the reporter gene was observed at the cerebral blood vessels and perivascular tissues. When the adenoviral vector was delivered into CSF of dogs suffering from subarachnoid hemorrhage, prominent expressions of transgene were observed. Introduction of the vector to the ischemic brain of rats provided efficient transgene expression in the peri-ischemic area. Therefore, gene transfer to the cerebral blood vessel and brain may be a promising approach for gene therapy of stroke. Atherosclerotic lesion plays an important role in stroke. We evaluated efficacy of adenovirus-mediated gene transfer to the atherosclerotic vessels from monkeys and rabbits using an ex vivo gene transfer system. Efficiency of transgene expression in the atherosclerotic endothelium was better than that of normal vessels in both animals. Thus, the endothelium of atherosclerotic vessels may be a good target for gene therapy. Next, we transfected atherosclerotic carotid arteries from rabbits with an adenoviral vector encoding endothelial nitric oxide synthase (eNOS). After overexpression of eNOS in the atherosclerotic arteries, the response to acetylcholine was augmented, showing similar relaxation with normal vessels. These results suggest that gene transfer to atherosclerotic vessels improves endothelial function, which may be a new therapeutic approach for cerebrovascular disease.
Details
- Title: Subtitle
- Adenovirus-mediated gene transfer to cerebral circulation
- Creators
- Hiroaki Ooboshi - Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidahi 3-1-1, Higashi-ku, Fukuoka 812-8582, JapanSetsuro Ibayashi - Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidahi 3-1-1, Higashi-ku, Fukuoka 812-8582, JapanDonald D Heistad - Department of Internal Medicine, University of Iowa College of Medicine, Iowa, IA, USAMasatoshi Fujishima - Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidahi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
- Resource Type
- Journal article
- Publication Details
- Mechanisms of ageing and development, Vol.116(2), pp.95-101
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/S0047-6374(00)00123-8
- PMID
- 10996009
- ISSN
- 0047-6374
- eISSN
- 1872-6216
- Language
- English
- Date published
- 2000
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040254302771
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