Journal article
Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension
Gene therapy, Vol.9(2), pp.110-117
2002
DOI: 10.1038/sj.gt.3301633
PMID: 11857069
Abstract
Gene transfer may be appropriate for therapeutic protocols targeted at the vascular endothelium. Endothelial dysfunction is the principal phenotype associated with atherosclerosis and hypertension. Oxidative stress has been implicated in the development of endothelial dysfunction. We have explored the ability of overexpressing anti-oxidant genes (superoxide dismutases; SODs) in vitro and in vivo to assess their potential for reversing endothelial dysfunction in a rat model, the stroke-prone spontaneously hypertensive rat (SHRSP). Western blotting and immunofluorescence assays in vitro showed efficient overexpression of MnSOD and ECSOD with respect to localisation to the mitochondria and extracellular surface, respectively. Transgene functional activity was quantified with SOD activity assays. MnSOD and ECSOD overexpression in intact SHRSP vessels in vivo led to endothelial and adventitial overexpression. Pharmacological assessment of transduced vessels following in vivo delivery by basal NO availability quantification demonstrated that the ‘null’ adenovirus and MnSOD adenovirus did not significantly increase NO availability. However, AdECSOD-treated carotid arteries showed a significant increase in NO availability (1.91 ± 0.04 versus 0.75 ± 0.08 g/g, n = 6, P = 0.029). In summary, efficient overexpression of ECSOD, but not MnSOD in vivo, results in improved endothelial function in a rat model of hypertension and has important implications for the development of endothelial-based vascular gene therapy.
Details
- Title: Subtitle
- Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension
- Creators
- J. P FENNELL - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United KingdomM. J BROSNAN - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United KingdomA. J FRATER - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United KingdomC. A HAMILTON - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United KingdomM. Y ALEXANDER - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United KingdomS. A NICKLIN - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United KingdomD. D HEISTAD - Departments of Internal Medicine and Program in Gene Therapy, University of Iowa College of Medicine and VA Medical Center, Iowa City, IA, United StatesA. H BAKER - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United KingdomA. F DOMINICZAK - BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United Kingdom
- Resource Type
- Journal article
- Publication Details
- Gene therapy, Vol.9(2), pp.110-117
- DOI
- 10.1038/sj.gt.3301633
- PMID
- 11857069
- NLM abbreviation
- Gene Ther
- ISSN
- 0969-7128
- eISSN
- 1476-5462
- Publisher
- Nature Publishing Group; Basingstoke
- Language
- English
- Date published
- 2002
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040585902771
Metrics
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