Catheter-mediated delivery of adenoviral vectors expressing β-adrenergic receptor kinase C-terminus inhibits intimal hyperplasia and luminal stenosis in rabbit iliac arteries
✍ Scribed by Zhengyu Luo; Maria Palasis; Midori Yamakawa; Louis X. Liu; Karen A. Vincent; Leonard Trudell; Geoffrey A. Akita; Walter J. Koch; Seng H. Cheng; Richard J. Gregory; Canwen Jiang
- Book ID
- 102337582
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 313 KB
- Volume
- 6
- Category
- Article
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.592
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✦ Synopsis
Abstract
Background
Previous studies have shown that incubation of balloon‐injured rat carotid arteries with adenoviral vectors encoding the carboxyl terminus of the β‐adrenergic receptor kinase (Ad2/βARKct) for 30 min reduces neointima formation. However, it is unclear whether this beneficial effect of βARKct could be achieved using a catheter‐based vector delivery system and whether the observed inhibition of neointima formation translated into a reduction of vessel stenosis.
Methods
In this study, Ad2/βARKct was infused into the balloon‐injured site of rabbit iliac arteries using a porous infusion catheter over 2 min. Twenty‐eight days after gene transfer, angiographic and histological assessments were performed.
Results
Angiographic and histological assessments indicate significant (p < 0.05) inhibition of iliac artery neointima formation and lumen stenosis by Ad2/βARKct. Our studies demonstrate that an inhibitory effect of Ad2/βARKct on neointima formation is achievable using a catheter‐based vector delivery system and that the inhibition of neointima formation translates into a gain in the vessel minimal luminal diameter. The extent of inhibition (35%) was comparable to that observed with adenoviral‐mediated expression of thymidine kinase plus ganciclovir treatment, a cytotoxic gene therapy approach for restenosis.
Conclusions
These results suggest that adenoviral‐mediated gene transfer of βARKct is a clinically viable cytostatic gene therapy strategy for the treatment of restenosis. Copyright © 2004 John Wiley & Sons, Ltd.