title: Local adenoviral-mediated inducible nitric oxide synthase gene transfer inhibits neointimal formation in the porcine coronary stented model.
abstract: In this study the effect of local adenoviral-mediated delivery of inducible nitric oxide synthase on restenosis was evaluated in a porcine coronary stented model. Local gene transfer of recombinant adenoviral vectors that encode human inducible nitric oxide synthase (AdiNOS) was tested. Control vector (AdNull) lacked a recombinant transgene. Endoluminal delivery of 1.0 x 10(11) adenoviral particles was accomplished in 45 s using the Infiltrator catheter (Interventional Technologies, San Diego, CA). Coronary stents were deployed, oversized by a ratio of 1.2:1, in the treated segments immediately after gene transfer. Fourteen animals were sacrificed at day 28 to evaluate the effects of iNOS gene transfer on morphometric indices, and 4 animals were sacrificed at day 4 for detection of human iNOS expression by RT-PCR. iNOS mRNA was detected in six of eight iNOS-transferred arteries, whereas no expression of human iNOS was detected in the nontarget arteries. Morphometric analysis showed that iNOS transfer significantly reduced neointimal formation (3.41 +/- 1.12 mm(2) vs 2.14 +/- 0.68 mm(2), P < 0.05). We concluded that efficient intramural adenovirus-mediated iNOS transfer can be achieved by using Infiltrator catheters. iNOS gene transfer significantly reduces neointimal hyperplasia following stent injury.
authors.affiliation: Experimental Animal Laboratory, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA. wangk@ccf.org
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kessler
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
authors.forename: Farhad
authors.initials: F
authors.lastname: Forudi
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.forename: Khaldoun
authors.initials: K
authors.lastname: Tarakji
authors.forename: Melina
authors.initials: M
authors.lastname: Kibbe
authors.forename: Imre
authors.initials: I
authors.lastname: Kovesdi
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Brough
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D023921:Coronary Stenosis / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000473:pathology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007124:Immunoenzyme Techniques; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II