Local adenoviral-mediated inducible nitric oxide synthase gene transfer inhibits neointimal formation in the porcine coronary stented model.
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.
Wang
Kai
K
Experimental Animal Laboratory, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA. wangk@ccf.org
Kessler
Paul D
PD
Zhou
Zhongmin
Z
Penn
Marc S
MS
Forudi
Farhad
F
Zhou
Xiaorong
X
Tarakji
Khaldoun
K
Kibbe
Melina
M
Kovesdi
Imre
I
Brough
Douglas E
DE
Topol
Eric J
EJ
Lincoff
A Michael
AM
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*
D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II