Document Detail


Antisense basic fibroblast growth factor gene transfer reduces neointimal thickening after arterial injury.
MedLine Citation:
PMID:  9052566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To determine whether synthesis of endogenous basic fibroblast growth factor (bFGF) after arterial injury is critical to the intimal thickening response, intraluminal adenoviral gene transfer of an antisense bFGF (Ad.ASbFGF) transgene was used to inhibit the subsequent synthesis of bFGF protein after injury.
METHODS: Sprague-Dawley rats underwent balloon catheter carotid artery injury and in vivo gene transfer. Isolated segments of rat common carotid artery were infected with an adenoviral vector encoding an antisense bFGF transcript at concentrations of 2 x 10(9), 1 x 10(10), or 1 x 10(11) pfu/ml. Control rats were treated with either a control adenovirus encoding the beta-galactosidase gene, (Ad.lacZ), at 1 x 10(10), or 1 x 10(11) pfu/ml, or phosphate-buffered saline solution (vehicle). Two weeks after injury the rats were killed and perfusion-fixed. Cross-sectional areas of the carotid arterial intima and media were measured by planimetry, and the intima/media ratio (I/M) was calculated for each vessel.
RESULTS: The mean I/M for each Ad.ASbFGF group and controls were compared and the significance assessed by analysis of variance. At two weeks after injury, the highest dose of Ad.ASbFGF, 1 x 10(11) pfu/ml, resulted in a near total inhibition of thickening (I/M = 0.14 +/- 0.04, mean +/- SEM) when compared with phosphate-buffered saline solution alone (I/M = 0.99 +/- 0.07), or Ad.lacZ 1 x 10(10) pfu/ml (I/M = 1.01 +/- 0.10) control treatments (p < 0.01). A tenfold lower dose of Ad.ASbFGF, 1 x 10(10) pfu/ml, also caused significant reduction in intimal thickening (I/M = 0.39 +/- 0.07, p < 0.01). Treatment with 2 x 10(9) pfu/ml Ad.ASbFGF did not significantly limit intimal thickening (I/M = 0.72 +/- 0.12).
CONCLUSIONS: Inhibition of bFGF synthesis in vivo using an antisense RNA strategy significantly inhibits intimal thickening after arterial balloon injury. This study suggests that continued bFGF synthesis contributes to intimal thickening after arterial injury, and that antisense bFGF may represent an effective strategy in limiting restenosis after angioplasty.
Authors:
A K Hanna; J C Fox; D G Neschis; S D Safford; J L Swain; M A Golden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of vascular surgery     Volume:  25     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-03-26     Completed Date:  1997-03-26     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  320-5     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviruses, Human
Animals
Antisense Elements (Genetics) / genetics*
Balloon Dilation
Carotid Artery Injuries
Carotid Artery, Common / enzymology,  pathology
Fibroblast Growth Factor 2 / biosynthesis,  genetics*,  physiology*
Gene Transfer Techniques*
Male
Muscle, Smooth, Vascular / enzymology,  injuries,  pathology
Rats
Rats, Sprague-Dawley
Transgenes
Tunica Intima / pathology*
beta-Galactosidase / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
HL02939/HL/NHLBI NIH HHS; HL26831/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antisense Elements (Genetics); 103107-01-3/Fibroblast Growth Factor 2; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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