Document Detail


Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart.
MedLine Citation:
PMID:  10527767     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most patients with severe coronary artery disease have normal baseline myocardial blood flow. Therefore, interventions aimed at inducing therapeutic angiogenesis in these patients should cause new blood vessel growth in the heart in the absence of chronic ischemia. It was examined whether adenovirus-mediated gene transfer of recombinant, secreted acidic fibroblast growth factor (sp+aFGF(1-154)), next to a major epicardial artery, may induce neovascularization and reduce the risk region for myocardial infarction upon coronary ligation near the injection site. Fifteen days prior to coronary artery occlusion, rabbits were treated with intramyocardial injections of AdCMV.sp+aFGF(1-154), the control vector AdCMV.NLSbetagal (1 x 10(9) plaque-forming units), or saline. Messenger RNA transcripts for aFGF(1-154) were present up to 12 days after injection in the tissues exposed to AdCMV.aFGF(1-154). Following coronary artery occlusion rabbits treated with AdCMV. sp+aFGF(1-154) showed a 50% reduction of the risk region for myocardial infarction (P < 0.01 vs control). Histologic analysis showed a twofold increase in length density of intramural coronary arterioles (P < 0.01 vs control) and a 17% increase in length density of the capillary network (P < 0.001) in the myocardium exposed to AdCMV.sp+aFGF(1-154). Thus, gene therapy with AdCMV. sp+aFGF(1-154) can induce angiogenesis in the absence of chronic ischemia. The newly formed collateral blood vessels provide an anatomical basis for the reduction in the risk region for myocardial infarction upon subsequent occlusion of the coronary artery in proximity of the site where angiogenesis was induced.
Authors:
J Safi; A F DiPaula; T Riccioni; J Kajstura; G Ambrosio; L C Becker; P Anversa; M C Capogrossi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Microvascular research     Volume:  58     ISSN:  0026-2862     ISO Abbreviation:  Microvasc. Res.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-10     Completed Date:  1999-12-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0165035     Medline TA:  Microvasc Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  238-49     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Affiliation:
Laboratory of Cardiovascular Science, National Institutes of Health, Baltimore, Maryland 21224, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Animals
Collateral Circulation / genetics
Coronary Disease / pathology,  therapy
Disease Models, Animal
Fibroblast Growth Factor 1 / genetics*,  physiology
Gene Expression
Gene Transfer Techniques*
Genetic Vectors
Humans
Male
Myocardial Infarction / prevention & control
Neovascularization, Physiologic / genetics*
RNA, Messenger / genetics,  metabolism
Rabbits
Chemical
Reg. No./Substance:
0/RNA, Messenger; 104781-85-3/Fibroblast Growth Factor 1

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