Published Online
on March 21, 2005

A more recent version of this article appeared on April 5, 2005

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Submitted on September 21, 2004
Revised on November 16, 2004
Accepted on November 19, 2004

Adenovirus-Mediated Expression of -Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs

Zhengyu Luo MD, Geoffrey Y. Akita DVM, PhD, Taro Date MD, PhD, Christopher Treleaven BSc, Karen A. Vincent PhD, Denise Woodcock AS, Seng H. Cheng PhD, Richard J. Gregory PhD, and Canwen Jiang MD, PhD^*

From Genzyme Corporation, Framingham, Mass.

^* To whom correspondence should be addressed. E-mail: canwen.jiang{at}genzyme.com.

Background--Hemodialysis vascular access dysfunction is the single most important cause of morbidity in kidney hemodialysis patients. Failure of an arteriovenous polytetrafluoroethylene (PTFE) graft, the most common form of hemodialysis access, is primarily due to intimal hyperplasia and thrombosis at the venous anastomosis.

Methods and Results--This study was aimed at evaluating the efficacy and safety of an adenoviral vector (Ad2/ARKct) encoding the carboxyl terminus of -adrenergic receptor kinase (ARKct) in a pig model of arteriovenous PTFE graft failure. Transduction of the external jugular vein with Ad2/ARKct (5E9, 5E10, or 5E11 particles per vein) did not result in systemic toxicity, as measured by clinical and pathological assessments. Ad2/ARKct significantly reduced neointimal hyperplasia in the graft/vein anastomosis. It also improved the graft patency rate and angiographic score, as measured histologically and angiographically, compared with vehicle or empty viral vector controls.

Conclusions--Our results suggest that local administration of adenoviral vectors encoding ARKct into the jugular vein represents a viable strategy to treat AV graft hemodialysis vascular access failure.

Key words: thrombosis • hyperplasia • grafting • hemodialysis • gene therapy

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				J. I. Rotmans, E. S.G. Stroes, G. Pasterkamp, Z. Luo, G. Y. Akita, T. Date, C. Treleaven, K. A. Vincent, D. Woodcock, S. H. Cheng, et al. Letter Regarding Article by Luo et al, "Adenovirus-Mediated Expression of {beta}-Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs" * Response Circulation, September 20, 2005; 112(12): e153 - e153. [Full Text] [PDF]