Linked Life Data

10559674

Source:http://linkedlifedata.com/resource/pubmed/id/10559674

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-12-9
pubmed:abstractText
Intravascular delivery of an E1/E3 deleted adenovirus encoding the hirudin protein reduces neointimal formation in the rat arterial injury model. Given the interspecies variability in response to adenoviral vectors, we tested this same construct in the hirudin-sensitive cholesterol-fed rabbit arterial balloon injury model. We hypothesized that local delivery of an E1/E3-deleted adenovirus encoding hirudin (Ad-Hir) in addition to early hirudin infusion would limit neointimal formation compared to early hirudin alone. Methods and Results: Local delivery of Ad-Hir, 2.5 x 10(10) PFU/ml, using a double balloon catheter [n = 6 vessels (v)] produced a 79% reduction in vessel wall thrombin activity at 48 h after balloon angioplasty (BA) compared with vehicle (Veh, n = 6v; p = 0. 05). In chronic experiments, hypercholesterolemic rabbits underwent femoral BA, and received either early hirudin alone (n = 9v) or early hirudin plus locally delivered Ad-Hir (early hirudin + Ad-Hir; n = 9v), an E1/E3-deleted adenovirus encoding beta-galactosidase (early hirudin + AdGal; n = 7v), or Veh (early hirudin + Veh; n = 10v). Early hirudin + Ad-Hir did not limit the arterial response to injury versus the other groups at 4 weeks after BA. Plaque area, cross-sectional luminal area narrowing by plaque, and T cell infiltration were significantly increased in the adenovirus- versus non-adenovirus-treated arteries. Plaque area correlated with T cell density. Conclusion: Following BA in cholesterol-fed rabbits, local transduction with A-Hir produced a marked reduction in vessel wall-associated thrombin activity. However, this strategy increased rather than decreased the arterial response to BA injury. Our results suggest that the lack of therapeutic effect resulted from adenovirus-stimulated plaque formation, possibly resulting from a T cell-mediated inflammatory response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1018-1172
pubmed:author
pubmed:copyrightInfo
Copyright 1999 S.Karger AG,Basel
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
343-52; discussion 430-3
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Local adenovirus-mediated delivery of hirudin in a rabbit arterial injury model.
pubmed:affiliation
Department of Medicine, Cardiovascular Division, University of Virginia Health Science Center, Charlottesville, VA 22908, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't