title: Adenovirus-mediated expression of beta-adrenergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs.
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.
  
  
  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.affiliation: Genzyme Corporation, Framingham, Mass 01701-9322, USA.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Luo
authors.forename: Geoffrey Y
authors.initials: GY
authors.lastname: Akita
authors.forename: Taro
authors.initials: T
authors.lastname: Date
authors.forename: Christopher
authors.initials: C
authors.lastname: Treleaven
authors.forename: Karen A
authors.initials: KA
authors.lastname: Vincent
authors.forename: Denise
authors.initials: D
authors.lastname: Woodcock
authors.forename: Seng H
authors.initials: SH
authors.lastname: Cheng
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gregory
authors.forename: Canwen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D002408:Catheters, Indwelling / Q000009:adverse effects; D004868:Equipment Failure; D005786:Gene Expression Regulation; D006083:Graft Occlusion, Vascular / Q000628:therapy*; D006965:Hyperplasia / Q000628:therapy*; D011138:Polytetrafluoroethylene / Q000627:therapeutic use*; D011943:Receptors, Adrenergic, beta / Q000008:administration & dosage*; D006435:Renal Dialysis; D013552:Swine; D014161:Transduction, Genetic; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D011943:Receptors, Adrenergic, beta; D011138:Polytetrafluoroethylene