Premium
Catheter‐mediated delivery of adenoviral vectors expressing β‐adrenergic receptor kinase C‐terminus inhibits intimal hyperplasia and luminal stenosis in rabbit iliac arteries
Author(s) -
Luo Zhengyu,
Palasis Maria,
Yamakawa Midori,
Liu Louis X.,
Vincent Karen A.,
Trudell Leonard,
Akita Geoffrey A.,
Koch Walter J.,
Cheng Seng H.,
Gregory Richard J.,
Jiang Canwen
Publication year - 2004
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.592
Subject(s) - neointima , restenosis , medicine , balloon catheter , gene delivery , genetic enhancement , intimal hyperplasia , stenosis , lumen (anatomy) , catheter , artery , beta adrenergic receptor kinase , receptor , stent , pathology , biology , surgery , gene , biochemistry , smooth muscle , g protein coupled receptor
Abstract Background Previous studies have shown that incubation of balloon‐injured rat carotid arteries with adenoviral vectors encoding the carboxyl terminus of the β‐adrenergic receptor kinase (Ad2/βARKct) for 30 min reduces neointima formation. However, it is unclear whether this beneficial effect of βARKct 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/βARKct 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/βARKct. Our studies demonstrate that an inhibitory effect of Ad2/βARKct 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 βARKct is a clinically viable cytostatic gene therapy strategy for the treatment of restenosis. Copyright © 2004 John Wiley & Sons, Ltd.