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 3 x 1010 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 AdCMV ceNoS-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: AdCMV ceNOS 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.
Original language | English (US) |
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Pages (from-to) | 1274-1281 |
Number of pages | 8 |
Journal | Circulation |
Volume | 97 |
Issue number | 13 |
DOIs | |
State | Published - Apr 7 1998 |
Keywords
- Genes
- Muscle
- Nitric oxide
- Smooth
- Stenosis
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)