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Adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs.
Circulation. 2005 Apr 05; 111(13):1679-84.Circ

Abstract

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/betaARKct) encoding the carboxyl terminus of beta-adrenergic receptor kinase (betaARKct) in a pig model of arteriovenous PTFE graft failure. Transduction of the external jugular vein with Ad2/betaARKct (5E9, 5E10, or 5E11 particles per vein) did not result in systemic toxicity, as measured by clinical and pathological assessments. Ad2/betaARKct 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 betaARKct into the jugular vein represents a viable strategy to treat AV graft hemodialysis vascular access failure.

Authors+Show Affiliations

Genzyme Corporation, Framingham, Mass 01701-9322, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15781730

Citation

Luo, Zhengyu, et al. "Adenovirus-mediated Expression of Beta-adrenergic Receptor Kinase C-terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs." Circulation, vol. 111, no. 13, 2005, pp. 1679-84.
Luo Z, Akita GY, Date T, et al. Adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs. Circulation. 2005;111(13):1679-84.
Luo, Z., Akita, G. Y., Date, T., Treleaven, C., Vincent, K. A., Woodcock, D., Cheng, S. H., Gregory, R. J., & Jiang, C. (2005). Adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs. Circulation, 111(13), 1679-84.
Luo Z, et al. Adenovirus-mediated Expression of Beta-adrenergic Receptor Kinase C-terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs. Circulation. 2005 Apr 5;111(13):1679-84. PubMed PMID: 15781730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs. AU - Luo,Zhengyu, AU - Akita,Geoffrey Y, AU - Date,Taro, AU - Treleaven,Christopher, AU - Vincent,Karen A, AU - Woodcock,Denise, AU - Cheng,Seng H, AU - Gregory,Richard J, AU - Jiang,Canwen, Y1 - 2005/03/21/ PY - 2005/3/23/pubmed PY - 2005/10/29/medline PY - 2005/3/23/entrez SP - 1679 EP - 84 JF - Circulation JO - Circulation VL - 111 IS - 13 N2 - 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/betaARKct) encoding the carboxyl terminus of beta-adrenergic receptor kinase (betaARKct) in a pig model of arteriovenous PTFE graft failure. Transduction of the external jugular vein with Ad2/betaARKct (5E9, 5E10, or 5E11 particles per vein) did not result in systemic toxicity, as measured by clinical and pathological assessments. Ad2/betaARKct 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 betaARKct into the jugular vein represents a viable strategy to treat AV graft hemodialysis vascular access failure. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15781730/Adenovirus_mediated_expression_of_beta_adrenergic_receptor_kinase_C_terminus_reduces_intimal_hyperplasia_and_luminal_stenosis_of_arteriovenous_polytetrafluoroethylene_grafts_in_pigs_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.CIR.0000160357.80517.92?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -