title: 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.affiliation: Genzyme Corporation, Framingham, MA 01701, USA.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Luo
authors.forename: Maria
authors.initials: M
authors.lastname: Palasis
authors.forename: Midori
authors.initials: M
authors.lastname: Yamakawa
authors.forename: Louis X
authors.initials: LX
authors.lastname: Liu
authors.forename: Karen A
authors.initials: KA
authors.lastname: Vincent
authors.forename: Leonard
authors.initials: L
authors.lastname: Trudell
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Akita
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
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*; D000792:Angiography; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D003251:Constriction, Pathologic / Q000517:prevention & control / Q000628:therapy*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006965:Hyperplasia / Q000473:pathology / Q000628:therapy*; D007083:Iliac Artery / Q000473:pathology*; D017434:Protein Structure, Tertiary; D011817:Rabbits; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*; D051552:beta-Adrenergic Receptor Kinases; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D017931:DNA Primers; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D001616:beta-Galactosidase