LOCAL ADENOVIRUS-MEDIATED TRANSFER OF HUMAN ENDOTHELIAL NITRIC-OXIDE SYNTHASE REDUCES LUMINAL NARROWING AFTER CORONARY ANGIOPLASTY IN PIGS

Citation
O. Varenne et al., LOCAL ADENOVIRUS-MEDIATED TRANSFER OF HUMAN ENDOTHELIAL NITRIC-OXIDE SYNTHASE REDUCES LUMINAL NARROWING AFTER CORONARY ANGIOPLASTY IN PIGS, Circulation, 98(9), 1998, pp. 919-926
Citations number
51
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Peripheal Vascular Diseas",Hematology,"Cardiac & Cardiovascular System
Journal title
ISSN journal
0009-7322
Volume
98
Issue
9
Year of publication
1998
Pages
919 - 926
Database
ISI
SICI code
0009-7322(1998)98:9<919:LATOHE>2.0.ZU;2-2
Abstract
Background-Nitric oxide, synthesized from L-arginine by nitric oxide s ynthase (NOS), is a vasodilator and inhibits vascular smooth muscle ce ll (SMC) proliferation and migration. The effects of local NOS gene tr ansfer on restenosis after experimental balloon angioplasty were inves tigated. Methods and Results-Left anterior descending coronary artery angioplasty was performed in 25 pigs. Animals received an intramural i njection of adenovirus (1.5x10(9) pfu) carrying either the NOS cDNA (A dCMVceNOS) or no cDNA (AdRR5) via the Infiltrator. Local gene transfer efficiency and bioactivity of recombinant protein were assessed after 4 days. Indices of restenosis were evaluated by computerized planimet ry on coronary artery sections prepared 28 days after angioplasty. Ade noviral vectors permitted efficient gene delivery to medial SMCs and a dventitial cells of coronary arteries. Vascular cGMP levels were depre ssed after angioplasty from 1.30+/-0.42 to 0.33+/-0.20 pmol/mg protein (P<0.05) but were restored after constitutive endothelial (ce) NOS ge ne transfer to 1.82+/-0.98 pmol/mg (P<0.05 versus injured group and P= NS versus control). The ratio of the neointimal area to the internal e lastic lamina fracture length, maximal neointimal thickness, and perce nt stenosis were all reduced in AdCMVceNOS- versus AdRR5-transduced pi gs (0.59+/-0.14 versus 0.80+/-0.19 mm, P=0.02; 0.75+/-0.21 versus 1.04 +/-0.25 mm, P=0.019; and 53+/-15% versus 75+/-11%, P=0.006, respective ly). Lumen area was significantly larger (0.70+/-0.35 mm(2) in AdCMVce NOS versus 0.32+/-0.18 mm(2) in AdRR5, P=0.007). Conclusions-Percutane ous adenovirus-mediated NOS gene transfer resulted in efficient local overexpression of functional NOS after angioplasty in coronary arterie s. Restored NO production in injured coronary arteries significantly r educed luminal narrowing, most likely through a combined effect on neo intima formation and on vessel remodeling after angioplasty.