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Oxidative stress, resulting from a deregulated equilibrium between superoxide and nitric oxide (NO) production, contributes to the progression of different vascular diseases such as atherosclerosis, hypertension, ischemia/reperfusion injury and restenosis. Despite disappointing results of various oral antioxidant treatment trials, promising findings have been reported using gene delivery of enzymes to improve NO bioavailability and decrease oxidative stress in animal models for vascular diseases. NO production can be increased by overexpression of endothelial NO synthase (eNOS) in the vascular wall. However, the complex regulation of NOS needs to be carefully considered in the context of gene therapy along with the availability of its cofactor tetrahydrobiopterin and eNOS uncoupling. Furthermore, preclinical studies demonstrated that gene delivery of antioxidative vascular wall-specific enzymes, such as heme oxygenase-1, superoxide dismutase, catalase and glutathione peroxidase, has the potential to attenuate oxidative stress and inhibit atherosclerosis. Another option is to transfect vascular disease patients with secreted antioxidants such as high density lipoprotein-associated enzymes or soluble scavenger receptors. The advantage of the latter is that gene delivery of these enzymes and receptors does not need to be endothelium specific. Nonetheless, techniques to deliver genes specifically to the vascular wall are under development and hold interesting perspectives for the treatment of vascular diseases in the future. The patents relevant to gene delivery are also discussed in this review article.

Type

Journal article

Journal

Recent Pat Cardiovasc Drug Discov

Publication Date

05/2011

Volume

6

Pages

89 - 102

Keywords

Animals, Antioxidants, Gene Transfer Techniques, Genetic Therapy, Humans, Nitric Oxide, Oxidation-Reduction, Oxidative Stress, Patents as Topic, Superoxides, Vascular Diseases