Catheter-mediated delivery of adenoviral vectors expressing beta-adrenergic receptor kinase C-terminus inhibits intimal hyperplasia and luminal stenosis in rabbit iliac arteries.

Abstract

BACKGROUND:

Previous studies have shown that incubation of balloon-injured rat carotid arteries with adenoviral vectors encoding the carboxyl terminus of the beta-adrenergic receptor kinase (Ad2/betaARKct) for 30 min reduces neointima formation. However, it is unclear whether this beneficial effect of betaARKct 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/betaARKct 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/betaARKct. Our studies demonstrate that an inhibitory effect of Ad2/betaARKct 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 betaARKct is a clinically viable cytostatic gene therapy strategy for the treatment of restenosis.

• Authors: 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
• Journal: The journal of gene medicine (J Gene Med) Vol. 6 Issue 10 Pg. 1061-8 (Oct 2004) ISSN: 1099-498X [Print] England
• PMID: 15386742 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2004 John Wiley & Sons, Ltd.

Chemical References

• DNA Primers
• Cyclic AMP-Dependent Protein Kinases
• beta-Adrenergic Receptor Kinases
• beta-Galactosidase

Topics

• Adenoviridae (genetics)
• Angiography
• Animals
• Carotid Arteries (pathology)
• Constriction, Pathologic (prevention & control, therapy)
• Cyclic AMP-Dependent Protein Kinases (chemistry, genetics)
• DNA Primers (chemistry)
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Genetic Vectors
• Hyperplasia (pathology, therapy)
• Iliac Artery (pathology)
• Protein Structure, Tertiary
• Rabbits
• Time Factors
• Tunica Intima (pathology)
• beta-Adrenergic Receptor Kinases
• beta-Galactosidase (metabolism)