Title: Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats
Authors: Janssens, Stefan ×
Flaherty, D
Nong, Z
Varenne, O
Van Pelt, N
Haustermans, Karin
Zoldhelyi, P
Gerard, R
Collen, Desire #
Issue Date: Apr-1998
Series Title: Circulation vol:97 issue:13 pages:1274-81
Abstract: BACKGROUND: Loss of endothelial NO production after arterial injury may contribute to restenosis, characterized by neointima formation and elastic recoil. Adenovirus-mediated transfer of the gene encoding NO synthase (NOS) in balloon-injured arteries may restore NO production and inhibit neointima formation. METHODS AND RESULTS: After balloon injury, rat carotid arteries were transduced with 3x10(10) pfu/mL recombinant adenovirus carrying the human endothelial constitutive NOS cDNA (AdCMVceNOS, n=8) or no cDNA (AdRR5, n=8). ceNOS expression was confirmed by immunoblot analysis of vascular extracts and was localized by immunostaining in 30% of medial smooth muscle cells (SMCs) and in the adventitia of AdCMVceNOS-transduced arteries. Vascular cGMP levels were reduced from 3.9 pmol/g wet wt in uninjured arteries to 0.7 pmol cGMP/g after AdRR5 but were restored after ceNOS gene transfer (3.8 pmol cGMP/g wet wt, P<.05 versus AdRR5). Intima-to-media ratio 2 weeks after injury was significantly reduced (0.19+/-0.02 in AdCMVceNOS-infected versus 0.69+/-0.07 in AdRR5-infected arteries, P<.05). In vitro, BrdU incorporation of AdCMVceNOS-infected SMCs was reduced by 28% compared with AdRR5-infected SMCs. Transduced cells from injured carotid arteries subjected to FACS sorting showed a significantly lower BrdU labeling index in ceNOS-infected rats (29+/-6% versus 43+/-5% and 45+/-4% in control, injured, and AdRR5-infected rats, respectively, P<.05). CONCLUSIONS: AdCMVceNOS gene transfer to balloon-injured rat carotid arteries restores vascular NO production and reduces neointima formation, at least in part because of an antiproliferative effect on medial SMCs. Adenovirus-mediated ceNOS gene transfer might reduce arterial restenosis after balloon angioplasty.
ISSN: 0009-7322
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Laboratory of Experimental Radiotherapy
× corresponding author
# (joint) last author

Files in This Item:
File Status SizeFormat
23799_1274.pdf Published 473KbAdobe PDFView/Open


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science